Immunotherapy

A clean room at CNRI.

CellBuilder: A ready-made solution for cell & gene therapy manufacturing

A clean room at CNRI.

With CellBuilder and our global partnerships, Children’s National hopes to expand access to groundbreaking cell and gene therapy treatments as they take off in the next five years.

With cell and gene therapies poised to reshape cancer and rare disease treatments, researchers at Children’s National Hospital are pioneering ready-to-use solutions that will bring these cutting-edge therapies directly to hospitals and other treatment centers, shrinking the distance between doctors and patients.

“The next five years are going to be a period of tremendous growth for cell and gene therapy,” said Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National. “Currently, there’s no shortage of interest from the medical community, but there’s a shortage of people who can manufacture and administer this care. We’re looking for ways to get these treatments to the patients by providing other institutions the tools they need to launch these programs cost-effectively, safely and efficiently.”

Called CellBuilder, the starter kits for cell and gene therapy programs could transform the landscape for pediatric patients.

The big picture

Dr. Hanley and many members of the Children’s National team have been working in cell and gene therapy for more than a decade, gaining extensive experience in the technical and regulatory hurdles inherent in creating treatments that target diseases at their source.

In cell therapy, a specific cell type is modified and transferred to a patient with a payload that can target a disease or disorder. For example, T cells may be modified and delivered to patients to teach their immune systems to fight cancer.  In gene therapy, a patient’s genetic code is modified to treat or prevent diseases, such as sickle cell disease, cancers and other genetic disorders. This can be done by introducing a healthy copy of a gene, repairing a faulty gene or altering a gene’s function.

Children’s National has become a leader in manufacturing virus-specific T cells, one method of delivering cell therapies, and the Cellular Therapy Program has conducted consortium-led, multi-center trials. Many other healthcare sites across the country want to start programs offering this care at their facilities.

The holdup in the field

Starting a cell and gene therapy program from scratch can take years of effort, training and money. That’s why Jay Tanna, M.S., R.A.C., quality assurance manager of the Cellular Therapy Program at Children’s National, said the team is creating CellBuilder starter kits, which include the manufacturing protocol and the resources necessary to launch a cell therapy program almost instantly.

“With a suitable knowledge base, institutions can start their own cellular therapy program at the point of care, using our manufacturing protocols, vetted reagents and other key elements of the process,” Tanna said. “Of course, interested institutions would have to meet regulatory requirements and establish a clean room to manufacture these therapies. If they want to use CellBuilder to run a clinical trial, they can do that. If they want to take it to become a licensed product, they can do that, too.”

Children’s National has worked with more than five institutions to build their virus-specific T-cell program and is now using the kits to accelerate and commercialize the process to increase patient access. The lab has also entered into a memorandum of understanding with the Tokyo-based Hitachi Global Life Solutions, Inc., an innovative modular clean room manufacturer, with the goal of offering a bundled solution.

Why we’re excited

Dr. Hanley and his colleagues say that the partnerships Children’s National is forging as they consult with other experts in this field will expand access to cell and gene therapy across the country—and hopefully around the world.

“It used to be that, to get a CAR T cell, you would collect the cells at Children’s National, ship them to a company like Novartis, have the therapy manufactured there and then shipped back,” said Michael Keller, M.D., who co-led a first-of-its kind immunotherapy trial as the Translational Research Laboratory director at the Children’s National Cell Enhancement and Technologies for Immunotherapy Program. “It was expensive, time-consuming and limited patient access. Now, there’s growing interest in manufacturing at each site, just like you would with a bone marrow transplant.”

With CellBuilder and our global partnerships, Children’s National hopes to expand access to groundbreaking cell and gene therapy treatments as they take off in the next five years, extending lifetimes and improving the quality of life for children suffering from rare disorders.

“We’re trying to capture the momentum underway in the field by providing this kit so that institutions don’t have to know how to do everything,” Dr. Hanley said. “We provide all the knowledge, a reagent list and everything else they need—and they provide the care.”

coronavirus and DNA

Untangling the root of long COVID with research

Alexandra Yonts, M.D.

Understanding and treating long COVID is still in its early days, but Dr. Yonts is beginning to see trends, along with hope for symptom relief.

A child who forgets the alphabet or spends 20 hours a day on the sofa will get a pediatrician’s attention. In late 2020, a stream of post-COVID patients just like this started presenting in the clinic of Alexandra Yonts, M.D., an infectious diseases specialist at Children’s National Hospital. Dr. Yonts quickly recognized the need to understand these patients and worked with hospital leadership to open the Pediatric Post-COVID Program, putting her at the forefront of clinicians and researchers investigating the disorder.

Understanding and treating long COVID is still in its early days, but Dr. Yonts is beginning to see trends, along with hope for symptom relief. She will present detailed data from a retrospective study of 254 post-COVID patients at the 2024 Children’s National-NIAID annual symposium, A New Paradigm: Infection-Associated Chronic Illnesses Affecting Children. She’ll discuss her findings on the patients’ symptoms at presentation, trajectory over time and a cluster analysis of symptom grouping. She gave an overview of her research and clinical work to Innovation District.

Q: What are you seeing in the Pediatric Post-COVID Program?

A: In the Infectious Diseases clinic, we had historically seen about one patient a month with prolonged fatigue or other persistent symptoms after an infection. Yet when COVID started, we noticed an increase in those patients. By late 2020, the numbers were increasing significantly, along with an uptick in appointment requests. We knew we needed to start a Pediatric Post-COVID Program, which launched in May 2021.

From the beginning and continuing to this day, severe fatigue is the most common reason kids come to our clinic, as is the case with adults. This ranges from marathon runners who can’t run a half-mile to those sleeping on the couch for 20 hours a day. We’re still researching the factors affecting this wide spectrum of symptoms.

Cognitive issues — often referred to as brain fog — are also significant. These can be seen as attention issues, such as difficulty remembering the alphabet in younger children or focusing in class for older children. Many kids have gastrointestinal problems like nausea, vomiting and abdominal pain. There’s also a prevalence of dysautonomia, affecting functions like blood pressure and heart rate, often seen in conditions like POTS (postural orthostatic tachycardia syndrome).

Initially, we saw kids infected early in the pandemic who had symptoms for 15 to 20 months. Our peak referrals were in 2022 after the Omicron variant, when we had a six-month waitlist. Although COVID cases have decreased, we still see kids with long-standing symptoms who have seen multiple providers without success. That’s why we’re here.

Q: Where are we in our understanding of long COVID, and where do we need to go?

A: We have lots of data but don’t know how it fits together yet. Research shows ongoing immune reactions to viral particles, with some patients having spike antigen in their blood or stool long after infection. There’s also evidence of autoimmunity and endovascular dysfunction, but we don’t yet understand the connections. It seems like viral persistence might be the underlying problem, but we haven’t pinpointed it yet.

Q: How important is it for the community to come together for events like the Children’s National-NIAID symposium?

A: It’s absolutely critical. We need researchers, clinicians and patients to collaborate. Researchers bring scientific expertise, clinicians provide practical insights and patients share their lived experiences and priorities. Conversations like the Children’s National-NIAID symposium are crucial for collaboration, thoughtful study design, advocacy and building connections with the patient community to make them feel validated and heard.

Learn more at the Children’s National-NIAID symposium on Sept. 5, by registering here.

Catherine Bollard, M.D., M.B.Ch.B., director of the Children’s National Center for Cancer and Immunology Research.

Closing the ‘Valley of Death’: Pioneering – and paying for – new therapies

Catherine Bollard, M.D., M.B.Ch.B., director of the Children’s National Center for Cancer and Immunology Research

“To cure brain tumors, sickle cell disease and scores of other illnesses that have an outsized impact on pediatric patients, we will need an innovative mechanism to ensure that money is not a barrier to scientific advancement and world-class care,” says Dr. Bollard.

With the advent of life-changing cell and gene therapies (CGTs) to treat pediatric diseases, price is becoming a significant obstacle to care and cures.

Successful therapies can wind up shelved or in hard-to-reach clinical trials for a litany of reasons: high manufacturing costs, significant regulatory burdens, a lack of enthusiasm from the pharmaceutical industry in the small pediatric market and the simple fact that insurance companies resist paying the price of $1 million or more for a therapeutic. When successful treatments are set aside and become victims of this market failure, leaders in pediatric medicine say the drug has been relegated to the “Valley of Death.”

Experts at Children’s National Hospital and other leading U.S. research institutions are working to ferry drugs across it.

A new way forward

The Access4Kids think tank is bringing together healthcare leaders to chart another way – with its hosts Catherine Bollard, M.D., M.B.Ch.B., director of the Children’s National Center for Cancer and Immunology Research, Crystal Mackall, M.D., director of the Stanford Center for Cancer Cell Therapy, Julie Park, M.D., Oncology Department chair at St. Jude Children’s Research Hospital, and Alan Wayne, M.D., pediatrician-in-chief at Children’s Hospital Los Angeles. Organized at the Children’s National Research & Innovation Campus, the think tank will include voices from Seattle Children’s Hospital in Washington state and the Moonshot Presidential Office in Washington, D.C., along with experts from academic institutions, the federal government and patient advocacy groups.

They explained their vision in their recent Nature Medicine perspective,  “Enhancing pediatric access to cell and gene therapies.” One idea under consideration is to create a biotech enterprise – backed by public monies, foundations and philanthropies – to support the late-stage development and commercialization of pediatric CGTs. Called a Pediatric Advanced Medicines Biotech (PAMB), this new organization would follow a novel pathway outside the traditional biopharma development model.

“To cure brain tumors, sickle cell disease and scores of other illnesses that have an outsized impact on pediatric patients, we will need an innovative mechanism to ensure that money is not a barrier to scientific advancement and world-class care,” Dr. Bollard said. “My colleagues and I aren’t exaggerating when we say this is a ‘save the world’ effort. It’s an initiative to disrupt the pharmaceutical industry and impact medicine, ultimately saving lives and entire lifetimes.”

The think tank is the second in a series aimed at solving this formidable challenge. Led by scientists, the work goes to the heart of healthcare economics.

“We need to find a way to support the academic ecosystem by reducing costs, creating efficiencies in manufacturing and working with regulatory bodies to bolster business models that lead to safe and effective therapeutics,” Dr. Mackall said. “We went to school to study science and medicine. Now, our mission includes revamping business models, as we find ways to increase access to lifesaving treatments for children in need.”

Why it matters

Creating novel pathways to pay for CGTs presents a challenge and an opportunity for researchers in pediatrics and rare diseases. Drs. Mackall, Bollard and their colleagues are exasperated when scientists discover successful treatments for life-threatening illnesses, but market forces lock the drug away in hard-to-reach clinical trials or – even worse – land it on a shelf.

Consider just one example, laid out in the Nature Medicine perspective: Children with adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) lack nearly all protection from viruses, bacteria and fungi, leaving them vulnerable to a world of opportunistic organisms. Researchers at San Raffaele Telethon Institute for Gene Therapy in Italy won U.S. and European regulatory approvals for a gene replacement therapy to treat the life-threatening disorder. Yet currently the therapy is only available in clinical trials, with support from research grants, philanthropic donations and institutional resources.

“This happens to successful therapeutics, and it’s heartbreaking. The current business model in medicine can lead to situations where successful therapies have extremely restricted availability, and there are no built-in guarantees of sustained access,” Dr. Bollard said. “We can and must do better – and we believe we have a way forward.”

teenager receiving an intravenous infusion

Novel cell therapy treatments offer promise to immune-compromised children

teenager receiving an intravenous infusion

In a first-of-its-kind clinical trial, researchers found that intravenous therapies made from virus-specific T-cells (VST) can effectively treat immunocompromised pediatric patients, far surpassing the current standard of care, according to new research published in Nature Communications.

More than 60% of patients in the phase 2 clinical trial led by investigators from Children’s National Hospital and Huntsman Cancer Institute responded to the innovative VST therapy. This new treatment uses blood from healthy donors to manufacture a highly specialized immune therapy that, when given to immune-compromised patients, prompts their immune system to fight off potentially life-threatening viruses, including cytomegalovirus, Epstein-Barr and adenovirus. Without this therapy, estimates suggest that less than 30% of patients would recover, using standard protocols.

“A vast majority of our patients not only responded to the therapy, but they were able to come off their antivirals, which come with extensive side effects,” said Michael Keller, M.D., the paper’s first author and the Translational Research Laboratory director at the Children’s National Cell Enhancement and Technologies for Immunotherapy (CETI) program. “This promising data suggests hope for patients with rare immune-compromising diseases that leave them vulnerable to so much in the world.”

The study brings together experts from the Pediatric Transplantation and Cell Therapy Consortium (PTCTC) and the Primary Immune Deficiency Treatment Consortium (PIDTC) to create the first multi-center, pediatric-consortium trial of adoptive T-cell therapies for viruses. It also represents one of the first to include critically ill patients, who are often excluded from research.

Children’s National leads the way

Working alongside Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research (CCIR), Dr. Keller and the CCIR team helped build an internationally recognized program, pioneering therapies to prevent complications from viral infections in immunocompromised patients. This includes patients with congenital immune deficiency and others who have undergone bone marrow transplantation for malignancies or non-malignant conditions, such as sickle cell disease.

While doctors can treat some immune-compromised patients for infections with standard antivirals, a small fraction don’t respond. Children’s National is one of a handful of hospitals in the country that has options. Over the last several decades, researchers have found ways to develop VST therapies made from banked T-cells, a more advanced application of how donated red blood cells are used to treat anemia.

In 2017, Drs. Keller and Bollard started collaborating with Michael Pulsipher, M.D.—now with Intermountain Primary Children’s Hospital and the Huntsman Cancer Institute at the University of Utah—to create a multi-institute clinical study. They combined the expertise at Children’s National in producing and banking cell therapy products with the community built around the PTCTC. Ultimately, they launched a clinical trial that was open to 35 centers in the U.S., enrolling 51 patients at 22 hospitals from 2018-2022.

“We wanted to prove that this potentially life-saving therapy could be given safely at regional pediatric centers that had never been able to use this approach before,” said Dr. Pulsipher, who served as the study’s co-principal investigator with Dr. Keller. “We united top experts in this area from the PTCTC and PIDTC and successfully treated some of the most challenging patients ever treated with this approach. Our findings helped define who can benefit the most from this therapy, paving the way for commercial development.”

The Good Manufacturing Practices (GMP) laboratory at Children’s National, led by Patrick Hanley, Ph.D., provided suitable VST therapies for 75 of 77 patients who requested to join the study. Clinical responses were achieved in 62% of patients who underwent stem cell transplants and in 73% of patients who were treated with VST and evaluated one month after their infusion. The paper laid out risks and clinical factors impacting outcomes when third-party donors are used to manufacture the VST therapies.

What’s ahead

Given that researchers are only beginning to develop cell therapies, work remains to understand the many ways they interact with the immune system. In a separate paper also recently published in Nature Communications, members of the multi-institute team documented a case of an infant with severe combined immune deficiency, who faced extremely rare side effects when the VST treatment interfered with her donor bone marrow graft. The case led the team to work with the Food and Drug Administration to identify criteria for VST donors enrolled in this study to mitigate complications.

In the decade ahead, Dr. Bollard sees promise in cell therapies for patients with cancer, immune deficiencies after transplant and dozens of other disorders, including genetic and autoimmune diseases. “Future studies will continue to look at ways to optimize the manufacturing, the administration and the long-term outcomes for these therapies—and to enhance the lifelong impact on our patients,” she said. “When we pair human ingenuity with the power of technology, I see tremendous potential.”

Acknowledgments: This study was funded with a nearly $5 million grant from the California Institute of Regenerative Medicine and was run through the operations center at the Children’s Hospital of Los Angeles, where Dr. Pulsipher was formerly on faculty.

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Children’s National in the News: 2023

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Explore some of the notable medical advancements and stories of bravery that defined 2023, showcasing the steadfast commitment of healthcare professionals at Children’s National Hospital and the resilient spirit of the children they support. Delve into our 2023 news highlights for more.

1. COVID during pregnancy dramatically increases the risk of complications and maternal death, large new study finds

According to a study published in British Medical Journal Global Health, women who get COVID during pregnancy are nearly eight times more likely to die and face a significantly elevated risk of ICU admission and pneumonia. Sarah Mulkey, M.D., prenatal-neonatologist neurologist, discussed findings based on her work with pregnant women and their babies.
(Fortune)

2. Rest isn’t necessarily best for concussion recovery in children, study says

A study led by Christopher Vaughan, Psy.D., pediatric neuropsychologist, suggests that — despite what many people may presume — getting kids back to school quickly is the best way to boost their chance for a rapid recovery after a concussion.
(CNN)

3. Pediatric hospital beds are in high demand for ailing children. Here’s why

David Wessel, M.D., executive vice president, chief medical officer and physician-in-chief, explained that one reason parents were still having trouble getting their children beds in a pediatric hospital or a pediatric unit after the fall 2022 respiratory surge is that pediatric hospitals are paid less by insurance.
(CNN)

4. Anisha Abraham details impact of social media use on children: ‘True mental health crisis’

Anisha Abraham, M.D., M.P.H., chief of the Division of Adolescent and Young Adult Medicine, joined America’s Newsroom to discuss the impact social media access has had on children’s mental health.
(FOX News)

5. Saving Antonio: Can a renowned hospital keep a boy from being shot again?

After 13-year-old Antonio was nearly killed outside his mom’s apartment, Children’s National Hospital went beyond treating his bullet wounds. Read how our Youth Violence Intervention Program team supported him and his family during his recovery.
(The Washington Post)

6. Formerly conjoined twins reunite with doctors who separated them

Erin and Jade Buckles underwent a successful separation at Children’s National Hospital. Nearly 20 years later they returned to meet with some of the medical staff who helped make it happen.
(Good Morning America)

7. Asthma mortality rates differ by location, race/ethnicity, age

Shilpa Patel, M.D., M.P.H., medical director of the Children’s National IMPACT DC Asthma Clinic, weighed in on a letter published in Annals of Allergy, Asthma & Immunology, asserting that the disparities in mortality due to asthma in the United States vary based on whether they occurred in a hospital, ethnicity or race and age of the patient.
(Healio)

8. How one Afghan family made the perilous journey across the U.S.-Mexico border

After one family embarked on a perilous journey from Afghanistan through Mexico to the U.S.-Mexico border, they eventually secured entry to the U.S. where Karen Smith, M.D., medical director of Global Services, aided the family’s transition and provided their daughter with necessary immediate medical treatment.
(NPR)

9. When a child is shot, doctors must heal more than just bullet holes

With the number of young people shot by guns on the rise in the U.S., providers and staff at Children’s National Hospital are trying to break the cycle of violence. But it’s not just the physical wounds though that need treating: young victims may also need help getting back on the right track — whether that means enrolling in school, finding a new group of friends or getting a job.
(BBC News)

10. This 6-year-old is a pioneer in the quest to treat a deadly brain tumor

Callie, a 6-year-old diagnosed with diffuse intrinsic pontine glioma, was treated with low-intensity focused ultrasound (LIFU) at Children’s National Hospital and is the second child in the world to receive this treatment for a brain tumor. LIFU is an emerging technology that experts like Hasan Syed, M.D., and Adrianna Fonseca, M.D., are trialing to treat this fatal childhood brain tumor.
(The Washington Post)

11. F.D.A. approves sickle cell treatments, including one that uses CRISPR

The FDA approved a new genetic therapy, giving people with sickle cell disease new opportunities to eliminate their symptoms. David Jacobsohn, M.B.A., M.D., confirmed that Children’s National Hospital is one of the authorized treatment centers and talked about giving priority to the sickest patients if they are on Vertex’s list.
(The New York Times)

12. 6-year-old fulfils wish to dance in the Nutcracker

After the potential need for open-heart surgery threatened Caroline’s Nutcracker performance, Manan Desai, M.D., a cardiac surgeon, figured out a less invasive procedure to help reduce her recovery time so she could perform in time for the holidays.
(Good Morning America)

2023 with a lightbulb

The best of 2023 from Innovation District

2023 with a lightbulbAdvanced MRI visualization techniques to follow blood flow in the hearts of cardiac patients. Gene therapy for pediatric patients with Duchenne muscular dystrophy. 3D-printed casts for treating clubfoot. These were among the most popular articles we published on Innovation District in 2023. Read on for our full list.

1. Advanced MRI hopes to improve outcomes for Fontan cardiac patients

Cardiac imaging specialists and cardiac surgeons at Children’s National Hospital are applying advanced magnetic resonance imaging visualization techniques to understand the intricacies of blood flow within the heart chambers of children with single ventricle heart defects like hypoplastic left heart syndrome. The data allows surgeons to make critical corrections to the atrioventricular valve before a child undergoes the single ventricle procedure known as the Fontan.
(3 min. read)

2. Children’s National gives first commercial dose of new FDA-approved gene therapy for Duchenne muscular dystrophy

Children’s National Hospital became the first pediatric hospital to administer a commercial dose of Elevidys (delandistrogene moxeparvovec-rokl), the first gene therapy for the treatment of pediatric patients with Duchenne muscular dystrophy (DMD). Elevidys is a one-time intravenous gene therapy that aims to delay or halt the progression of DMD by delivering a modified, functional version of dystrophin to muscle cells.
(2 min. read)

3. New model to treat Becker Muscular Dystrophy

Researchers at Children’s National Hospital developed a pre-clinical model to test drugs and therapies for Becker Muscular Dystrophy (BMD), a debilitating neuromuscular disease that is growing in numbers and lacks treatment options. The work provides scientists with a much-needed method to identify, develop and de-risk drugs for patients with BMD.
(2 min. read)

4. First infants in the U.S. with specially modified pacemakers show excellent early outcomes

In 2022, five newborns with life-threatening congenital heart disease affecting their heart rhythms were the first in the United States to receive a novel modified pacemaker generator to stabilize their heart rhythms within days of birth. Two of the five cases were cared for at Children’s National Hospital. In a follow-up article, the team at Children’s National shared that “early post-operative performance of this device has been excellent.”
(2 min. read)

5. AI: The “single greatest tool” for improving access to pediatric healthcare

Experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere came together to discuss how pediatric specialties can use AI to provide medical care to kids more efficiently, more quickly and more effectively at the inaugural symposium on AI in Pediatric Health and Rare Diseases, hosted by Children’s National Hospital and the Fralin Biomedical Research Institute at Virginia Tech.
(3 min. read)

6. AAP names Children’s National gun violence study one of the most influential articles ever published

The American Academy of Pediatrics (AAP) named a 2019 study led by clinician-researchers at Children’s National Hospital one of the 12 most influential Pediatric Emergency Medicine articles ever published in the journal Pediatrics. The findings showed that states with stricter gun laws and laws requiring universal background checks for gun purchases had lower firearm-related pediatric mortality rates but that more investigation was needed to better understand the impact of firearm legislation on pediatric mortality.
(2 min. read)

7. Why a colorectal transition program matters

Children’s National Hospital recently welcomed pediatric and adult colorectal surgeon Erin Teeple, M.D., to the Division of Colorectal and Pelvic Reconstruction. Dr. Teeple is the only person in the United States who is board-certified as both a pediatric surgeon and adult colorectal surgeon, uniquely positioning her to care for people with both acquired and congenital colorectal disease and help them transition from pediatric care to adult caregivers.
(3 min. read)

8. First-of-its-kind holistic program for managing pain in sickle cell disease

The sickle cell team at Children’s National Hospital received a grant from the Founders Auxiliary Board to launch a first-of-its-kind, personalized holistic transformative program for the management of pain in sickle cell disease. The clinic uses an inter-disciplinary approach of hematology, psychology, psychiatry, anesthesiology/pain medicine, acupuncture, mindfulness, relaxation and aromatherapy services.
(3 min read)

9. Recommendations for management of positive monosomy X on cell-free DNA screening

Non-invasive prenatal testing using cell-free DNA (cfDNA) is currently offered to all pregnant women regardless of the fetal risk. In a study published in the American Journal of Obstetrics and Gynecology, researchers from Children’s National Hospital provided context and expert recommendations for maternal and fetal evaluation and management when cfDNA screening is positive for monosomy X or Turner Syndrome.
(2 min. read)

10. Innovation in clubfoot management using 3D anatomical mapping

While clubfoot is relatively common and the treatment is highly successful, the weekly visits required for Ponseti casting can be a significant burden on families. Researchers at Children’s National Hospital are looking for a way to relieve that burden with a new study that could eliminate the weekly visits with a series of 3D-printed casts that families can switch out at home.
(1 min. read)

11. Gender Self-Report seeks to capture the gender spectrum for broad research applications

A new validated self-report tool provides researchers with a way to characterize the gender of research participants beyond their binary designated sex at birth. The multi-dimensional Gender Self-Report, developed using a community-driven approach and then scientifically validated, was outlined in a peer-reviewed article in the American Psychologist, a journal of the American Psychological Association.
(2 min. read)

12. Cardiovascular and bone diseases in chronic kidney disease

In a study published by Advances in Chronic Kidney Disease, a team at Children’s National Hospital reviewed cardiovascular and bone diseases in chronic kidney disease and end-stage kidney disease patients with a focus on pediatric issues and concerns.
(1 min. read)

The international NexTGen team

NexTGen team assembles to delve into progress on CAR T-cell therapies

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The international NexTGen team assembled at the Children’s National Research & Innovation Campus for their annual meeting to share progress made in their first full year of work on the $25-million Cancer Grand Challenge, focused on creating a CAR T-cell therapy for pediatric solid tumors.

“It was invigorating to bring the whole team together from our eight institutions in the U.S., U.K. and France, as we uncover opportunities in our research and share the headway that we have made,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research and interim chief academic officer at Children’s National Hospital. “Breakthroughs happen when Team Science collaborates, and that is exactly what is happening here with the NexTGen team.”

Why we’re excited

Over the course of two days, more than 85 team members met to discuss the six work packages that are coming together, with the ambitious goal of making CAR T-cell therapies the standard of care for solid tumors within the next decade:

  • Discovery of new targets
  • The tumor microenvironment
  • Component engineering
  • Integration and modeling
  • Clinical studies
  • Data integration

Each work package includes a patient advocate – individuals with a personal connection to cancer as a family member or survivor – who offers their invaluable perspectives on the research and treatment process. Many attended the meeting, sitting alongside the oncologists, immunologists, mathematicians, molecular biologists and other leading experts.

The big picture

The Cancer Grand Challenges are funded by grants from the National Cancer Institute, Cancer Research U.K. and the Mark Foundation for Cancer Research. Their goal is to drive progress against cancer by empowering global leaders in the research community to take on tough challenges and think differently.

“They call it a ‘grand challenge’ for a reason,” Dr. Bollard said. “It’s going to take the effort and expertise of all these individuals to make a new therapy a reality. I have confidence that we can do it.”

Auditorium at the Cell and Gene Therapy in the DMV Symposium

Cell & Gene Therapy in the DMV: Experts collaborate for cures

Leaders in medicine, academia, industry and state and local government came together for the first annual Cell and Gene Therapy in the DMV Symposium, hosted at the Children’s National Research & Innovation Campus. The mission: Connect the local scientific community – bursting with expertise and collaboration potential – to develop these cutting-edge therapies for cancers, sickle cell disease and immune-mediated disorders.

The daylong event drew over 100 experts from a range of organizations in the D.C, Maryland and Virginia region, sometimes called the DMV: Children’s National Hospital, the Food and Drug Administration, the National Institute of Standards and Technology, the National Institutes of Health, the General Accounting Office, Virginia Tech, MaxCyte, AstraZeneca, Kite Pharma, Montgomery College, the Maryland State Department of Commerce and more. Together, they unraveled a host of topics including the regulatory environment, workforce development and training, research standards and the promise of these therapies.

“Our Cell & Gene Therapy Symposium brings together our current collaborators and future partners in the D.C., Maryland and Virginia space, which is an incredibly rich area. We see tremendous opportunity and breakthroughs in our future,” said Catherine Bollard, M.D., M.B.Ch.B., interim chief academic officer and chief of Pediatrics at Children’s National Hospital. “Many different diseases rely on the immune system to either be ramped up or to be controlled, and we can seize on these biological processes. Cell and gene therapies are at the heart of where medicine is going.”

The big picture

For decades, oncologists largely have turned to the same menu of treatments to fight cancer, including surgery, chemotherapy and radiation. Cell and gene therapies offer the promise of training the immune system to fight diseases with fewer side effects and potentially higher success rates. Early work has shown progress in liquid cancers, like leukemia, raising the possibility that the therapies could be used on solid tumors and other disorders, such as lupus and sickle cell disease. However, many disciplines must come together to yield discoveries.

“Nobel Prize-winning work doesn’t necessarily translate into available therapies for patients. It takes a whole community like this to make it happen,” said Cenk Sumen, chief scientific officer at MaxCyte Inc., an international cell engineering company based in Rockville, Md. “It has been exciting to see this diverse group of stakeholders come together, which is probably unmatched anywhere on the planet.”

Why we’re excited

Symposium host Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National, said the goal was to cement the region as the No. 1 location for this highly technical research and development. He believes Children’s National can offer essential elements to this success, given its clinical and research expertise, workforce training opportunities and geographic proximity to the scientific leadership of the federal government. “What makes us unique is our proximity to all the players who can help create new treatment options for patients. We truly are the biomedical capital of the world,” he said.

Michael Friedlander, vice president for health sciences at Virginia Tech, notes that the earliest stages of invention will emanate from academic labs including those at Virginia Tech and Children’s National. “You have basic scientists who are doing fundamental research on properties and procedures that will lead to the new therapies of tomorrow,” he said. “We are putting in place the fundamental pieces to advance children’s health in all dimensions.”

What’s ahead

One challenge is developing a workforce to help prepare cell therapies for patients, following precise standards to ensure the therapy works as designed. Children’s National does this training, as do others in the region. Lori Kelman, Ph.D., M.B.A., biotechnology coordinator and professor at Montgomery College, said that the area is full of people who want to help people and who like science.

“The thing that people might not know is that you don’t need a Ph.D. to work in cell and gene therapy,” she said. “There are opportunities at all levels, including the entry level, which is where a great career often starts.”

ARPA-H logo

Children’s National selected as member of ARPA-H Investor Catalyst Hub spoke network

ARPA-H logoThe hospital will advocate for the unique needs of children as part of nationwide network working to accelerate transformative health solutions.

Children’s National Hospital was selected as a spoke for the Investor Catalyst Hub, a regional hub of ARPANET-H, a nationwide health innovation network launched by the Advanced Research Projects Agency for Health (ARPA-H).

The Investor Catalyst Hub seeks to accelerate the commercialization of groundbreaking and accessible biomedical solutions. It uses an innovative hub-and-spoke model designed to reach a wide range of nonprofit organizations and Minority-Serving Institutions, with the aim of delivering scalable healthcare outcomes for all Americans.

“The needs of children often differ significantly from those of adults. This partnership reflects our commitment to advancing pediatric healthcare through innovation and making sure we’re addressing those needs effectively,” said Kolaleh Eskandanian, Ph.D., M.B.A., vice president and chief innovation officer at Children’s National. “Leveraging the strength of this hub-and-spoke model, we anticipate delivering transformative solutions to enhance the health and well-being of the patients and families we serve.”

Children’s National joins a dynamic nationwide network of organizations aligned to ARPA-H’s overarching mission to improve health outcomes through the following research focus areas: health science futures, proactive health, scalable solutions and resilient systems. Investor Catalyst Hub spokes represent a broad spectrum of expertise, geographic diversity and community perspectives.

“Our spoke network embodies a rich and representative range of perspectives and expertise,” said Mark Marino, vice president of Growth Strategy and Development for VentureWell and project director for the Investor Catalyst Hub. “Our spokes comprise a richly diverse network that will be instrumental in ensuring that equitable health solutions reach communities across every state and tribal nation.”

As an Investor Catalyst Hub spoke, Children’s National gains access to potential funding and flexible contracting for faster award execution compared to traditional government contracts. Spoke membership also offers opportunities to provide input on ARPA-H challenge areas and priorities, along with access to valuable networking opportunities and a robust resource library.

Drs. Robert Keating, Brian Rood and Catherine Bollard

Children’s National announces new professorships

Drs. Robert Keating, Brian Rood and Catherine Bollard

Robert Keating, M.D., Brian Rood, M.D., and Catherine Bollard, M.D., M.B.Ch.B.

Children’s National Hospital named Robert Keating, M.D., as the McCullough Distinguished Professor of Neurosurgery. He serves as the chief of neurosurgery and co-director of the high-intensity focused ultrasound (HIFU) program at Children’s National.

Children’s National Hospital named Brian Rood, M.D., as the Kurt D. Newman, M.D., Professor of Neuro-Oncology. He serves as director of clinical neuro-oncology and medical director of the Brain Tumor Institute at Children’s National.

Children’s National Hospital elevated Catherine Bollard, M.D., M.B.Ch.B., to the Dr. Robert J. and Florence T. Bosworth Distinguished Professor of Cancer and Transplantation Biology Research. She is the Interim Executive Vice President and Chief Academic Officer and Interim Director, Children’s National Research Institute. She also serves as the director of the Center for Cancer and Immunology Research and director of the Program for Cell Enhancement and Technologies for Immunotherapy at Children’s National.

About the awards

Professorships at Children’s National support groundbreaking work on behalf of children and their families and foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect the recipient’s achievements and donor’s forethought to advance and sustain knowledge. Children’s National is grateful for its generous donors, who have funded 47 professorships.

Dr. Keating is a longstanding leader in neurosurgery research and care. His areas of expertise include brain tumors, traumatic brain injuries, craniofacial anomalies, Chiari malformations and spinal dysraphism. With Dr. Keating’s leadership, the neurosurgery department is pioneering innovations such as HIFU, a non-invasive therapy using focused ultrasound waves to ablate a focal area of tissue. It can treat tumors located in difficult locations of the brain, movement disorders and epilepsy. Children’s National was one of the first pediatric hospitals in the nation to use HIFU for neuro-oncology patients.

“Our goal is to elevate our top-ranked program to even greater heights,” says Dr. Keating. “We will continue to use cutting-edge technology and non-invasive approaches to make the knife obsolete in pediatric neurosurgery and improve outcomes for children.”

Dr. Rood studies the biology of pediatric brain tumors. He focuses on protein signatures and biomarkers specific to different types of brain cancers. His study of neoantigens is informing the development of T-cell immunotherapies to target a tumor’s unique proteins.

“Immunotherapy is revolutionizing how we treat childhood brain tumors — safely, effectively and with the precision made possible by using a patient’s own cells,” says Dr. Rood. “This professorship enables our team to advance this revolution, which will save lives and improve lifetimes.”

Dr. Bollard received the Dr. Robert J. and Florence T. Bosworth Professor of Cancer and Transplantation Biology Research in 2018 to support her work to develop cell and gene therapies for patients with cancer and underlying immune deficiencies. Her professorship has been elevated to a distinguished professorship to amplify her research and celebrate her accomplishments in the field of immunotherapy.

About the donor

These appointments were made possible through an extraordinary $96 million investment from an anonymous donor family for rare pediatric brain tumor research and care. It is one of the hospital’s largest donations and will transform the hospital’s ability to give patients with rare brain cancer a better chance at healthy lifetimes.

The anonymous family brings a depth of compassion for children facing rare and often challenging diagnoses. Their partnership will immediately advance every aspect of our globally recognized leadership to create new, more effective treatments.

Their investment also endowed the Professorship in Molecular Neuropathology. We look forward to bestowing that honor on a Children’s National pediatric leader.

little girl with cancer

A destination for pediatric oncology care: Children’s National Hospital’s T-cell therapy trials

When children are diagnosed with pediatric cancer, most doctors are forced to reach for the same standard therapies that were available decades ago. Research oncologists at Children’s National Hospital are changing that with clinical trials that will hopefully train the body’s immune system – specifically its T cells – to fight the tumors.

Holly Meany, M.D., and her colleague Amy Hont, M.D., oncologists and research scientists at the Center for Cancer and Immunology Research, have put together a pair of clinical trials that are investigating two pathways for using T cells to go after solid tumors.

“At Children’s National, we have a novel immunotherapy to offer to patients with relapsed or refractory solid tumors,” said Meany, director of the Solid Tumor Program. “This is a patient population who has failed standard therapy, so new technologies and treatments are always needed in this group.”

Where we started

Meany’s trial laid the foundation. She began the center’s research using a patient’s own blood sample to develop a targeted therapy and evaluate the safety and efficacy of this approach. In her study, scientists isolated the T cells, grew millions in a lab and reinfused them into the patient. The cells were replicated in an environment that was rich in three proteins that are commonly found on the surface of solid tumor cancer cells.

“Our hope and hypothesis are that when we give the T cells back to the patient, those T cells circulate and hunt down the cancer cells that have the tumor proteins,” Meany said. “We are hoping to use the patient’s own immune system to attack the cancer in an enduring way.”

Where we are headed

Hont’s phase 1 trial, which is currently recruiting participants, builds on Meany’s work using a healthy donor whose T cells have not been impacted by chemotherapy or other treatments. The cells can be prepared, stored and readily available for patients who need them. They are also matched through specific proteins on the patient’s own cells to bolster their effectiveness. The participants in this trial have Wilms tumors, rhabdomyosarcoma, neurosarcoma, soft tissue sarcoma or neuroblastoma, but conventional therapies including chemotherapy, radiation or surgery were unable to fully treat the disease.

In both studies, Hont said that the T cells have been given in an outpatient setting with fewer side effects compared to other cancer treatments aimed at high-risk malignancies.

“This allows patients to really maintain a good quality of life during a particularly hard time,” Hont said. “Also, these T cells are designed to act in the body the way that our immune system acts in a physiologic way. This means patients typically don’t have the severe side effects that we think of with chemotherapy or other therapies.”

Children’s National leads the way

The team at Children’s National is one of the few in the country to offer this kind of T-cell therapy for solid tumors. “Immunotherapy has been challenging for this patient population because the tumors are adept at finding out ways to evade treatment,” Hont said. “Giving patients a chance to receive a targeted T-cell therapy, while also maintaining a high quality of life, is something that’s special here.”

x-ray of child with congenital heart disease

Cell therapy research for neuroprotection in congenital heart disease receives another $3.3 million from NIH

x-ray of child with congenital heart disease

Significant neurological delay is emerging as one of the most important current challenges for children with congenital heart disease, yet few treatment options are currently available.

The research lab of Nobuyuki Ishibashi, M.D., at Children’s National Hospital, recently received $3.3 million in additional funding for research into cell therapy for neuroprotection in children with congenital heart disease. The new support comes from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health.

The research goal

The overarching goal of the award is to establish detailed molecular signatures from critical cell populations for tissue repair and regeneration at single cell resolution after bone marrow-derived mesenchymal stromal cell (BM-MSC) delivery. The team has shown cellular, structural and behavioral improvements in pre-clinical models after delivery of BM-MSCs through cardiopulmonary bypass for children with congenital heart disease. However, the mechanisms underlying the therapeutic action of BM-MSCs still remain largely unknown. This R01 renewal will address the key knowledge gap.

Why it matters

Significant neurological delay is emerging as one of the most important current challenges for children with congenital heart disease, yet few treatment options are currently available.

The Ishibashi lab has demonstrated the efficacy and utility of using cardiopulmonary bypass to deliver BM-MSCs  to improve neurological impairments in children undergoing surgery for congenital heart disease. Most notably, this included development of a phase 1 clinical trial, MeDCaP, at Children’s National.

The big picture

Together with the ongoing clinical trial established from the previous award, identifying molecular signatures of BM-MSC treatment and mining specific BM-MSC exosomes for unique cardiopulmonary bypass pathology will significantly improve understanding of this cell-based treatment. This work will also provide a new therapeutic paradigm for potential cell-free MSC-based therapies for neuroprotection in children with congenital heart disease.

child in hospital bed

$96 million philanthropic investment will transform rare pediatric brain tumor research and care

child in hospital bedChildren’s National Hospital announced a $96 million investment from an anonymous donor family to transform rare childhood brain tumor research and care. The donation, which strengthens our globally recognized leadership in the field, is one of the largest in the hospital’s history.

Children’s National will harness the investment to recruit more top talent and advance the most promising research. This will produce safer, more effective treatments. It also will elevate standards of care to help children with rare brain tumors thrive for a lifetime.

The big picture

Brain tumors are the most common solid tumors affecting children. They are especially challenging in kids because their brains are still developing. The disease and current treatments can put them at risk for lifelong complications.

The anonymous family’s investment provides new hope for patients who face rare and often challenging brain tumor diagnoses — in the Washington, D.C., community and around the world.

“This incredible partnership will lift up one of the nation’s top pediatric brain tumor programs into the stratosphere,” said Kurt Newman, M.D., president and CEO of Children’s National. “It will immediately propel our best-in-class research and care, allowing us to bring new therapies to children with brain tumors. This fundamentally changes the healthcare journey and long-term outcomes for children and their families.”

Why it’s important

This transformational investment will have a far-reaching impact on our ability to save and improve the lives of children with brain tumors. Funds will fuel collaborative breakthroughs across a range of scientific and psychosocial approaches.

The partnership will supercharge highly individualized and promising treatments for children with brain tumors. We will radically transform the research landscape with a focus on:

  • Low intensity focused ultrasound (LIFU) – Advancing laboratory research and a clinical program designed to treat childhood brain tumors with LIFU therapy
  • Cellular immunotherapy – Testing new gene-engineered immune cell products and accelerating their integration into standards of care
  • Rare Brain Tumor Program – Propelling new clinical trials through the hospital’s national and global leadership in pediatric brain tumor consortia. Already, Children’s National is leading a new collaborative with hospitals in North America, South America and Europe to better understand and find novel treatments for these rare diseases
  • Neurosurgery innovation – Exploring multiple ways to perform safer, more effective neurosurgery and developing new methods to enhance drug/agent delivery
  • Precision medicine – Recruiting leading scientists to advance biology-informed therapies that can be targeted for children across a spectrum of brain tumors
  • Good Manufacturing Practices (GMP) facility – Expanding our GMP, one of the first standalone facilities at a children’s hospital in the country, to translate new discoveries into clinical trials more rapidly
  • Additional priorities including expansion of clinical research infrastructure and growth of bioinformatics, brain tumor repository and molecular diagnostics initiatives

The partnership also transforms how we approach care. It will power our pursuit of psychosocial, behavioral health and neuroscientific initiatives to help kids live well and cope with the unique circumstances of their diagnosis. We will focus on:

  • Lifetime health and wellness – Building a world-class research and clinical care program to shape a new paradigm for supporting a child’s physical and emotional health during and long after cancer treatment
  • Child Mental Health & Behavioral Brain Tumor Lab – Establishing a robust neuro-oncology mental health program that delivers timely interventions and specialized psychiatric care for patient well-being
  • Additional priorities including a new Neuroscience Nursing Excellence Program and growth of psychosocial support activities that bring comfort and encouragement to children during their treatment journey

Children’s National is proud to lead the way to a better future for pediatric rare brain tumor patients and expand our internationally recognized capabilities for neuro-oncology care.

U.S. News Badges

Children’s National Hospital ranked #5 in the nation on U.S. News & World Report’s Best Children’s Hospitals Honor Roll

U.S. News BadgesChildren’s National Hospital in Washington, D.C., was ranked #5 in the nation on the U.S. News & World Report 2023-24 Best Children’s Hospitals annual rankings. This marks the seventh straight year Children’s National has made the Honor Roll list. The Honor Roll is a distinction awarded to only 10 children’s hospitals nationwide.

For the thirteenth straight year, Children’s National also ranked in all 10 specialty services, with eight specialties ranked in the top 10 nationally. In addition, the hospital was ranked best in the Mid-Atlantic for neonatology, cancer, neurology and neurosurgery.

“Even from a team that is now a fixture on the list of the very best children’s hospitals in the nation, these results are phenomenal,” said Kurt Newman, M.D., president and chief executive officer of Children’s National. “It takes a ton of dedication and sacrifice to provide the best care anywhere and I could not be prouder of the team. Their commitment to excellence is in their DNA and will continue long after I retire as CEO later this month.”

“Congratulations to the entire Children’s National team on these truly incredible results. They leave me further humbled by the opportunity to lead this exceptional organization and contribute to its continued success,” said Michelle Riley-Brown, MHA, FACHE, who becomes the new president and CEO of Children’s National on July 1. “I am deeply committed to fostering a culture of collaboration, empowering our talented teams and charting a bold path forward to provide best in class pediatric care. Our focus will always remain on the kids.”

“I am incredibly proud of Kurt and the entire team. These rankings help families know that when they come to Children’s National, they’re receiving the best care available in the country,” said Horacio Rozanski, chair of the board of directors of Children’s National. “I’m confident that the organization’s next leader, Michelle Riley-Brown, will continue to ensure Children’s National is always a destination for excellent care.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals and recognizes the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News.

“For 17 years, U.S. News has provided information to help parents of sick children and their doctors find the best children’s hospital to treat their illness or condition,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “Children’s hospitals that are on the Honor Roll transcend in providing exceptional specialized care.”

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

The eight Children’s National specialty services that U.S. News ranked in the top 10 nationally are:

The other two specialties ranked among the top 50 were cardiology and heart surgery, and urology.

Eugene Hwang

Eugene Hwang, M.D., named as William Seamus Hughes Professor of Neuro-oncology and Immunology

Eugene HwangChildren’s National Hospital named Eugene Hwang, M.D., the inaugural William Seamus Hughes Professor of Neuro-oncology and Immunology. This professorship is the first at Children’s National to focus exclusively on these two pediatric specialties.

Dr. Hwang serves as associate chief of oncology, director of the Clinical Neuro-oncology Immunotherapeutics Program and director of the Neuro-oncology Fellowship Program. He is an associate professor of pediatrics at the George Washington University School of Medicine and Health Sciences.

About the award

Dr. Hwang joins a distinguished group of 42 Children’s National physicians and scientists who hold an endowed chair. Professorships at Children’s National support groundbreaking work on behalf of children and their families and foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect the recipient’s achievements and donor’s forethought to advance and sustain knowledge.

Dr. Hwang has dedicated much of his career to the pursuit of new therapies that improve outcomes for children with brain cancer. He has led many early phase clinical trials on immunotherapeutics, gene therapy and new targeted agents. He participates in international studies focused on reducing harmful side effects of standard treatments. He serves as the principal investigator for the Pediatric Brain Tumor Consortium and co-chairs their Immunotherapy Working Group. Dr. Hwang also lends his time to grant review committees and the scientific advisory boards of several large foundations.

Claire and Kevin Hughes, through their vision and generosity, are ensuring that Dr. Hwang and future holders of this professorship will launch new initiatives to rapidly advance the fields of pediatric neuro-oncology and immunotherapy, elevate our leadership and improve outcomes for children diagnosed with brain cancer.

About the donors

Claire and Kevin Hughes established this professorship with support from community partners in loving memory of their son William Seamus Hughes (Willie). Their dedication to giving all children a chance for life has helped launch groundbreaking trials and research at Children’s National, including one of the first trials in the U.S. to use cell therapy to treat brain tumors.

“Working with Willie meant working with a young man who embodied a resilient, cheerful spirit that was truly remarkable,” said Dr. Hwang. “It meant fighting side-by-side with a walking inspiration, who I continue to remember and who continues to drive the mission of curing childhood brain cancer. I’m deeply honored to ensure that Willie’s spirit and bravery lives on in the promise to other families that face a devastating brain tumor diagnosis.”

Abstract Happy 2022 New Year greeting card with light bulb

The best of 2022 from Innovation District

Abstract Happy 2022 New Year greeting card with light bulbA clinical trial testing a new drug to increase growth in children with short stature. The first ever high-intensity focused ultrasound procedure on a pediatric patient with neurofibromatosis. A low dose gene therapy vector that restores the ability of injured muscle fibers to repair. These were among the most popular articles we published on Innovation District in 2022. Read on for our full top 10 list.

1. Vosoritide shows promise for children with certain genetic growth disorders

Preliminary results from a phase II clinical trial at Children’s National Hospital showed that a new drug, vosoritide, can increase growth in children with certain growth disorders. This was the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature.
(2 min. read)

2. Children’s National uses HIFU to perform first ever non-invasive brain tumor procedure

Children’s National Hospital successfully performed the first ever high-intensity focused ultrasound (HIFU) non-invasive procedure on a pediatric patient with neurofibromatosis. This was the youngest patient to undergo HIFU treatment in the world.
(3 min. read)

3. Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Using a single injection of a low dose gene therapy vector, researchers at Children’s National restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle.
(3 min. read)

4. Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, was selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children.
(4 min. read)

5. New telehealth command center redefines hospital care

Children’s National opened a new telehealth command center that uses cutting-edge technology to keep continuous watch over children with critical heart disease. The center offers improved collaborative communication to better help predict and prevent major events, like cardiac arrest.
(2 min. read)

6. Monika Goyal, M.D., recognized as the first endowed chair of Women in Science and Health

Children’s National named Monika Goyal, M.D., M.S.C.E., associate chief of Emergency Medicine, as the first endowed chair of Women in Science and Health (WISH) for her outstanding contributions in biomedical research.
(2 min. read)

7. Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient

A team at Children’s National performed the first treatment with sonodynamic therapy utilizing low intensity focused ultrasound (LIFU) and 5-aminolevulinic acid (5-ALA) medication on a pediatric patient. The treatment was done noninvasively through an intact skull.
(3 min. read)

8. COVID-19’s impact on pregnant women and their babies

In an editorial, Roberta L. DeBiasi, M.D., M.S., provided a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field.
(2 min. read)

9. Staged surgical hybrid strategy changes outcome for baby born with HLHS

Doctors at Children’s National used a staged, hybrid cardiac surgical strategy to care for a patient who was born with hypoplastic left heart syndrome (HLHS) at 28-weeks-old. Hybrid heart procedures blend traditional surgery and a minimally invasive interventional, or catheter-based, procedure.
(4 min. read)

10. 2022: Pediatric colorectal and pelvic reconstructive surgery today

In a review article in Seminars in Pediatric Surgery, Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National, discussed the history of pediatric colorectal and pelvic reconstructive surgery and described the key advances that have improved patients’ lives.
(11 min. read)

Cancer cells

Searching for the key to treating neuroblastoma tumors in kids

Cancer cells

Jianhua Yang, Ph.D., has dedicated his research to finding the molecular mechanism of neuroblastoma development and is working to develop novel therapeutics.

There continues to be an urgent need to identify novel therapies for childhood cancers. Neuroblastoma (NB) is the most common malignant solid tumor in children and contributes to more than 15% of all pediatric cancer-related deaths. Despite strides made in chemotherapy treatment over the past 30 years, NB largely remains an incurable disease. That’s why Jianhua Yang, Ph.D., associate professor and research faculty at the Center for Cancer and Immunology Research at Children’s National Hospital, has dedicated his research to finding the molecular mechanism of NB development and is working to develop novel therapeutics to target molecules he and his team identify in the lab.

Q: What has driven you to do this research?

A: In order to design better and potentially more effective NB treatment approaches, we must further understand the mechanism that activates NB development. We don’t know what that mechanism is yet, and that’s what we’re working to unlock. I felt with my training in cell biology and immunology, I could use that background to help develop novel therapies.

The research is hard and can often times feel frustrating. But I feel I’m working on something that has the potential to make a huge difference. I tell the researchers I work with that you have to really believe in what we’re doing. We’re doing something very different. Before I moved to D.C. to join Children’s National, I sent a text to a former mentor to let him know I was joining the team here to continue my work. His reply said, “I’ve always had confidence in you,” and it’s that type of encouragement that drives me to keep going.

Q: What is your current focus in this area?

A: Specifically, we’re working on two targets right now:

  1. To define the role and regulation of CaM kinase-like vesicle-associated (CAMKV) in NB development and examining the therapeutic potential of CAMKV kinase inhibition for treating NB in pre-clinical models. We’ve found that CAMKV is highly expressed in NB tumor samples and its kinase activity is required for tumor growth. So, if we knock out this gene, tumor cells will die. We’re studying how it is being activated, and if we can find out what causes it, we can find a way to inhibit its activation. Targeting CAMKV is a novel concept for treating NB. CAMKV kinase inhibitors may serve not only as stand-alone therapies but also as effective adjuncts to current chemotherapeutic regimens treating this aggressive pediatric malignancy.
  2. To define the role and regulation of transmembrane protein 108 (TMEM108) in NB development and examine the therapeutic potential of TMEM108 functional blockade for treating NB in pre-clinical models. Evolutionarily, in human genome it has no other family member, it’s a loner. And if you knock it out in NB tumor cells, tumor cells will die. We’re learning how it functions through our basic research, which is quite difficult. But we’re thinking if we can find the antibody to bind to it and block its function, we could stop the tumor from growing or even cause the tumor to die.

Q: What excites you about doing this work within the Center for Cancer and Immunology Research?

A: At Children’s National, I’ll be able to combine my work with the incredible work in immunotherapy that Drs. Catherine Bollard and Muller Fabbri are doing. I’m excited to be here to have that strong collaboration with their labs to develop new therapies.

In the next 5 years, I feel we’ll be able to identify good blocking antibodies that we can then test combinations of to see how it blocks tumor growth. If we can find ways to combine that antibody therapy with traditional chemotherapy options, we can achieve a real cure for NB.

Learn more about the Center for Cancer and Immunology Research.

Drs. Bollard and Hanley

Research into a new way to combat solid tumors earns part of a $25M award

Drs. Bollard and Hanley

Catherine Bollard, M.D., M.B.Ch.B., and Patrick Hanley, Ph.D.

Children’s National Hospital has developed multi-antigen specific T cells that have shown success in pre-clinical models in attacking pediatric solid tumors. Now the promising area of research earned a major boost from the Cancer Grand Challenges — founded in 2020 by the two largest funders of cancer research in the world – Cancer Research UK and the National Cancer Institute in the U.S.

This award supported the foundation of NexTGen, a team of scientists and clinicians with expertise in immunology, proteomics, mathematics and more, across eight institutions in the U.S., U.K. and France. Catherine Bollard, M.B.Ch.B, M.D., director of the Center for Cancer and Immunology Research at Children’s National, and Martin Pule, M.D., clinical associate professor at the University College of London are the co-leads of this effort.

The NexTGen team is one of four Cancer Grand Challenges’ new teams, representing a total investment of $100M to diverse, global teams to take on some of the toughest challenges in cancer research. NexTGen will create a new approach that performs clinical and basic research together to facilitate real-time knowledge exchange from the lab to the clinic and back again.

While the more widely known CAR T-cells have made tremendous progress for patients with B-cell leukemias, lymphomas and other blood cancers, the CAR T-cell field has not made the same impact for adult and pediatric solid tumors.

“A tumor cell is very clever because it tries to hide from the immune system by deleting or down regulating targets that the T cell is directed towards,” said Dr. Bollard.

Dr. Bollard further discusses the importance of having patient voices during the decision-making process in this quest, her hopes for their program and the concept of the combining tumor antigen-specific T cells with CAR-T cells that her team will develop.

Q: Can you explain the NexTGen vision?

A: The overall vision is that we will have developed the next generation of cell therapies to cure children with refractory solid tumors by the end of the five years. It is important to move the field forward, so we wanted to be innovative in our approach to this grand challenge for these children who have no other therapeutic options left.

Q: What are the most three important components of this project?

A: First, science and diplomacy played a significant role in bringing in the right set of investigators from diverse scientific backgrounds. What started as a conversation using the universal language of science, it quickly became an international project to address this complex issue. Second, we worked very hard with our patient advocates during the writing process, and they will be working side by side with the investigators at the bench and clinic. Third, we were the only group to have clinical trials in our proposal starting very early in the grant funding period, which is unprecedented.

Q: Can you describe NexTGen’s research model?

A: From our experience in leukemia, we know that progress is greatly accelerated if discovery occurs hand-in-hand with clinical development. Therefore, unlike classical programs where years of pre-clinical discovery and developmental work is required before the clinical translation, we will take a non-conventional non sequential approach.

Specifically, in the NexTGen Program, clinical development will start early with three cutting-edge clinical studies evaluating engineered T-cell technologies that we have recently developed understanding that there are some questions that can ONLY be answered in the clinic. To that end, clinical and translational data from these clinical trials will be able to feed into and enrich the discovery and pre-clinical science throughout the NexTGen Program in a circular fashion to promote this research program that goes from bedside to bench and back.

Q: How is Children’s National leading the way?

A: Children’s National is leading one of the three clinical trials that combine our non-gene engineered tumor antigen-specific T-cell platform with gene engineered T cells to generate a novel T-cell therapy against relapsed /refractory solid tumors. Combining tumor antigen specific T cells with the CAR T-cell platform represents a novel concept that may have more potency against these hardest to treat tumors in children.

Q: Why is it so important to include the patient voice during the discussion and decision making?

A: Because we are also physicians and scientists, we do not forget the patient and their families. Thus, we have a robust patient advocacy group embedded in this vision. The group will co-develop summaries explaining the challenges NextGen will address, how this will be achieved and how results will be used, with major input in clinical trial design and consent documents as well as key input into how patient tissue samples can be used to facilitate research discoveries. The patient advocacy team will also help find broad representation from multiple geographical locations of advocates with lived experience of different cancer types, including bereaved relatives and cancer survivors. These and many more strategies applied with patient advocacy groups will elevate the call for a broader and accelerated adoption of CAR-T clinical trials to broaden access to all patients.

Q: What excites you most about this?

A: What excites me the most is working with this incredible group of scientists, physicians and patient advocates all with rich and deep expertise who bring together an extensive and diverse knowledge base. The fact that we will be all working together toward a common goal of curing pediatric solid tumors in the next five to 10 years is extraordinarily energizing. This sizeable international collaboration comprises the right talent to get this done. It is also highly exciting to simultaneously have three clinical trials running in parallel with the discovery science and the pre-clinical work. I am extremely optimistic that we will realize NexTGen’s vision to bring next generation engineered T-cell therapies to the routine care of children with solid tumors within a decade.

Dr. Bollard and her laboratory

Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

Dr. Bollard and her laboratory

Cancer Grand Challenges NexTGen team members (left to right): Amy Hont, M.D., AeRang Kim, M.D., Nitin Agrawal, Ph.D., Catherine Bollard, M.D., M.B.Ch.B., Conrad Russell Cruz, M.D., Ph.D., Patrick Hanley, Ph.D., and Anqing Zhang.

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, has been selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children. Cancer Grand Challenges is a global funding platform, co-founded by Cancer Research UK and the National Cancer Institute in the U.S., that supports a community of diverse, global teams to come together, think differently and take on some of cancer’s toughest challenges.

The Cancer Grand Challenges NexTGen team, co-led by University College London’s Martin Pule, M.D., will be working to develop next-generation cell therapies for children with solid cancers. Cancer is a leading cause of death by disease in children worldwide. Although survival has increased for some pediatric cancers, such as blood cancers, survival for some solid tumors has seen little improvement for more than 30 years. The team hopes to build a much deeper understanding of childhood cancers and develop and optimize novel therapies for children with solid tumors, ultimately hoping to improve survival and diminish the lifelong toxicities often experienced by survivors.

“With our Cancer Grand Challenge, we hope to bring next-generation CAR T-cell therapies to children with solid tumors,” said Dr. Bollard. “What excites me most is the energized, passionate group of people we’ve brought together to take this challenge on. Big problems remain to be addressed, but we believe they can be solved, and that we’re the team to solve them.”

“NexTGen represents crucial and overdue work. It has hope written all over,” said Sara Wakeling, patient advocate on the team and CEO and co-founder of Alice’s Arc, a children’s charity for rhabdomyosarcoma. “NexTGen hopes to transform the way these aggressive solid tumors are treated with less toxic side-effects, giving the children a real chance at growing up and realizing their potential. I’m so proud to be part of this exceptional team of scientists, clinicians and advocates who want to change the story for those diagnosed.”

The NexTGen team unites scientists and clinicians with expertise in immunology, proteomics, mathematics and more, across eight institutions throughout the U.S., U.K. and France. The Children’s National investigators that will also join are:

  • Nitin Agrawal, Ph.D., associate professor in the Center for Cancer and Immunology Research at Children’s National.
  • Conrad Russell Cruz, M.D., Ph.D.,principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies at Children’s National.
  • Patrick Hanley, Ph.D., chief and director of the cellular therapy program at Children’s National and leader of the Good Manufacturing Practices laboratory.
  • Amy Hont, M.D., oncologist in the Center for Cancer and Immunology Research at Children’s National.
  • AeRang Kim, M.D., oncologist in The Center for Cancer and Blood Disorders at Children’s National.
  • Holly Meany, M.D., oncologist in The Center for Cancer and Blood Disorders at Children’s National.
  • Anqing Zhang, biostatistician in the Biostatistics and Study Methodology Department at Children’s National.

The team, co-funded by Cancer Research UK, the National Cancer Institute and The Mark Foundation for Cancer Research, aims to bring much needed new treatments to children with solid cancers.

The NexTGen team is one of four new teams announced today as part of Cancer Grand Challenges, representing a total investment of $100m to diverse, global teams to take on some of the toughest challenges in cancer research.

“Cancer is a global issue that needs to be met with global collaboration. This investment in team science encourages diverse thinking to problems that have long hindered research progress,” said David Scott, Ph.D., director of Cancer Grand Challenges, Cancer Research UK. “Cancer Grand Challenges provides the multidisciplinary teams the time, space and funding to foster innovation and a transformative approach. NexTGen is one of four newly funded teams joining a scientific community addressing unmet clinical needs across cancer research.”

Find out more

Cancer Grand Challenges supports a global community of diverse, world-class research teams with awards of £20m/$25m to come together, think differently and take on cancer’s toughest challenges. These are the obstacles that continue to impede progress and no one scientist, institution or country will be able to solve them alone. Cancer Grand Challenges teams are empowered to rise above the traditional boundaries of geography and discipline.

Founded by the two largest funders of cancer research in the world – Cancer Research UK and the National Cancer Institute* in the U.S. – Cancer Grand Challenges aims to make the progress against cancer we urgently need. Cancer Grand Challenges currently supports more than 700 researchers and advocates across 10 countries, representing 11 teams are supported to take on 10 of the toughest challenges in cancer research.

The Cancer Grand Challenges NexTGen team, announced June 16, 2022, is taking on the initiative’s Solid Tumours in Children challenge. It is led by Dr. Bollard (Children’s National) and Dr. Pule (University College London), along with 23 co-investigators and 7 patient advocates, and is spread across eight institutions across the U.S., U.K. and France: Cardiff University; Children’s Hospital of Philadelphia; Children’s National Hospital; INSERM; the Institute of Cancer Research; Stanford Medicine; Stanford University; University College London. The Cancer Grand Challenges NexTGen team is funded by Cancer Research UK, the National Cancer Institute in the U.S. and The Mark Foundation for Cancer Research.

*The National Cancer Institute is part of the National Institutes of Health.

 

girl hugging stuffed animal

Developing next-generation T cells to fight cancer

girl hugging stuffed animal

In the last decade, researchers have witnessed significant advances in the immunotherapy field. Most recently, a study in Nature claimed a novel CAR T-cell therapy “cured” a patient.

In the last decade, researchers have witnessed significant advances in the immunotherapy field. Most recently, a study in Nature claimed a novel CAR T-cell therapy “cured” a patient. Given the landmark scientific achievement for patients with different types of leukemia and lymphoma, Children’s National Hospital experts chimed in on the technology they have developed beyond CAR T cells.

Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, discusses the implications of this research, how it relates to the work she’s doing at Children’s National and the future of T-cell therapies.

Q: What did the research published in Nature find?

A: It reported a decade-long experience with this novel T-cell therapy called CD19 CAR T cells. These were used to treat patients with a type of leukemia or lymphoma that expresses the CD19 on its surface. While the article reported the experience of Children’s Hospital of Philadelphia and the University of Pennsylvania, multiple groups throughout the country did similar trials that have used these unique CD19 CAR T cells to treat children and adults with these refractory blood cancers.

Q: What are your thoughts on the implications of this research?

A: We now have three FDA-approved commercial CD19 CAR T-cell products developed by several academic institutions. This is revolutionary for our patients who have B-cell leukemias and lymphomas. It’s incredibly exciting for our T-cell therapy field in general because this was the first time the FDA approved a T-cell therapy. What it means now is the field is extremely excited to develop similar effective therapies for other patients with cancer.

Q: How does this relate to your work at Children’s National?

A: While CAR T cells have made tremendous progress for patients with B-cell leukemias, lymphomas and other blood cancers, the CAR T-cell field has not made the same impact for adult and pediatric solid tumors. We think the field is going to expand the type of T-cell therapies we’re generating beyond just CAR T cells. That’s where the work we’re doing comes in – not only by developing new T cells that don’t need gene engineering but also T cells that can be used as a platform for next-generation engineering approaches. We think the technology we’ve developed at Children’s National will help make an impact, especially in the solid tumor space. I hope in the next 10 years, we’ll be having a conversation not just about CAR T cells, but about other types of T cells that are now making an impact for solid tumors.

Q: How are the CAR T cells you develop different than those in the Nature article?

A: We think our multi-antigen specific T cells are complimentary and could have more potency than conventional CAR T cells for solid tumors especially when used in combination. This is in part because they can identify multiple targets on a tumor cell. Tumor cells are very clever and try to hide from T-cell therapies by down regulating the target that the T cell is directed towards. However, our novel T-cell therapies get around that escape by targeting multiple targets in a single product, making it much harder for the cancer cell to hide from the immune attack by the T cells.

Additionally, we’re excited by our approach because not all of our products require gene engineering, unlike CAR T cells. We have effectively used our T cells to target viruses in the “off-the-shelf” setting and we’re now about to start a first human clinical trial at Children’s National using an off the shelf T-cell product for children with solid tumors. It makes the T-cell therapy more like an “off-the-shelf” drug therapy that will allow us to treat many more children and adults nationally, as well as we hope, internationally.