desktop computer showing the CNRI Annual Report

Driving pediatric breakthroughs through 2023

desktop computer showing the CNRI Annual ReportThe Children’s National Research Institute released its 2022-2023 Academic Annual Report. In the report, a summary of the past academic year highlights the accomplishments of each of the institute’s research centers, provides research funding figures and exalts some of the institute’s biggest milestones.

The stories in the report are a testament to the hard work and dedication of everyone at the Children’s National Research Institute.

We celebrated five decades of leadership and mentorship of Naomi Luban, M.D., and her incredible accomplishments in the W@TCH program, which have been instrumental in shaping the future of pediatric research.

We also celebrated innovation, highlighting our recent FDA award to lead a pediatric device consortium, which recognizes our commitment to developing innovative medical devices that improve the lives of children.

Breakthroughs at the Research & Innovation Campus continued as our researchers worked tirelessly to develop new treatments and therapies that will transform the lives of children and families around the world.

Taking a look at the breakthroughs happening in our now six research centers, we spotlighted the following stories:

  • Reflecting on decades of progress in the blood, marrow and cell therapy programs at Children’s National. Our researchers have made significant strides in this field, and we are proud to be at the forefront of these life-saving treatments.
  • In genetic medicine, we continue to be a beacon of hope for families facing rare and complex conditions. Our researchers are making incredible breakthroughs that are changing the landscape of pediatric medicine.
  • We are also proud to share the $90 million award received from an anonymous donor to support pediatric brain tumor research. The predominant focus of this award is to develop new treatments that will improve outcomes for children with this devastating disease.
  • This year, we opened a new Center that enhances our research capabilities in the field of Prenatal, Neonatal & Maternal Health Research. We are excited about the possibilities this new center will bring and look forward to the discoveries that will emerge from it.
  • In addition, we are driving future pandemic readiness with the NIH funded Pediatric Pandemic Network. Our researchers are using cutting-edge technology and innovative approaches to prepare for the next pandemic and protect children.
  • We are also exploring the potential of artificial intelligence (AI) in pediatric breakthroughs. Our researchers are using machine learning and other AI techniques to develop new treatments and therapies that will transform the lives of children.
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.”

Winners of the International Conference on Medical Image Computing and Computer Assisted Intervention

AI team wins international competition to measure pediatric brain tumors

Winners of the International Conference on Medical Image Computing and Computer Assisted Intervention
Children’s National Hospital scientists won first place in a global competition to use artificial intelligence (AI) to analyze pediatric brain tumor volumes, demonstrating the team’s ground-breaking advances in imaging and machine learning.

During the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), the Children’s National team demonstrated the most accurate algorithm to study the volume of brain tumors – the most common solid tumors affecting children and adolescents and a leading cause of disease-related death at this young age. The technology could someday help oncologists understand the extent of a patient’s disease, quantify the efficacy of treatments and predict patient outcomes.

“The Brain Tumor Segmentation Challenge inspires leaders in medical imaging and deep learning to try to solve some of the most vexing problems facing radiologists, oncologists, computer engineers and data scientists,” said Marius George Linguraru, D.Phil., M.A., M.Sc., the Connor Family Professor in Research and Innovation and principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation. “I am honored that our team won, and I’m even more thrilled for our clinicians and their patients, who need us to keep moving forward to find new ways to treat pediatric brain tumors.”

Why we’re excited

With roughly 4,000 children diagnosed yearly, pediatric brain tumors are consistently the most common type of pediatric solid tumor, second only to leukemia in pediatric malignancies. At the urging of Linguraru and one of his peers at the Children’s Hospital of Philadelphia, pediatric data was included in the international competition for the first time, helping to ensure that children are represented in medical and technological advances.

The contest required participants to use data from multiple institutions and consortia to test competing methods fairly. The Children’s National team created a method to tap into the power of two types of imaging and machine learning: 3D convolutional neural network and 3D Vision Transformer-based deep learning models. They identified regions of the brain affected by tumors, made shrewd data-processing decisions driven by the team’s experience in AI for pediatric healthcare and achieved state-of-the-art results.

The competition drew 18 teams who are leaders from across the AI and machine learning community. The runner-up teams were from NVIDIA and the University of Electronic Science and Technology of China.

The big picture

“Children’s National has an all-star lineup, and I am thrilled to see our scientists recognized on an international stage,” said interim Executive Vice President and Chief Academic Officer Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer for Immunology Research. “As we work to attack brain tumors from multiple angles, we continue to show our exceptional ability to create new and better tools for diagnosing, imaging and treating these devastating tumors.”

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.

teen parents with baby

Community-wide program to support teen parents serves as a model for engagement

More than 500 adolescent mothers, caregivers and community members benefitted from a coordinated “collective impact” model to provide support aimed at addressing the litany of strains faced by teen parents, according to a case study published Wednesday in the journal Pediatrics.

Known as the District of Columbia Network for Parenting and Expectant Teens (DC NEXT), the model used well-tested pillars of community organization to provide services and care that bolstered the well-being of pregnant and expectant teens in the city. The case study found that the 3-year-old program, which included teen advisors to help guide the mission, could serve as a model in other areas with high rates of teen parents.

“There’s no system of care for teen parents in Washington, D.C., or really anywhere in our country,” said Yael Smiley, M.D., Children’s National Hospital pediatrician and the study’s lead author. “Our coalition came together to connect the resources and the people who care about young parents and their families to improve their health, their outcomes, their well-being, and set them up for success. We fuse representatives from healthcare, education and housing policy — people who care about creating the very best outcomes possible.”

The patient benefit

More than 140,000 teens became parents in 2021 in the United States. In Washington, D.C., more than 300 babies are born to teens each year, and the rate of births to young teens ages 15 to 17 is double the national average. These young parents often face barriers to childcare and education and poor birth outcomes, often stemming from a lack of access to prenatal care.

To address these obstacles, the network assembled a city-wide network in 2020 to follow the five pillars of an evidence-based “collective impact” model:

  • Create a common agenda
  • Design shared measurement systems
  • Host mutually reinforcing activities
  • Foster continuous communication
  • Rely on trusted backbone support

What’s unique

DC NEXT was housed at the District of Columbia Primary Care Association (DCPCA), which received the 3-year, $4.5 million federal grant and provided the leadership. At Children’s National, Dr. Smiley led a team that partnered with DCPCA and Howard University to direct a network of community clinics, nonprofits and other organizations whose mission was to support adolescent parents. Hundreds of client-facing staff members were trained to provide trauma-informed, human-centered care. DC NEXT also engaged directly with teen mothers through well-being surveys that led to improved access to essential programs, including resources for housing and food security. Over 550 young parents and caregivers have been impacted by the program.

The leadership quickly realized that the teen parents needed a voice and created a “context team” of paid teen advisors who provided insights into their unique experiences and needs as parents. They help set the agenda, choose program offerings and tailor communications to their peers.

“If the network can continue to grow and support young parents to achieve their health and well-being goals, the impact will be felt across generations,” said Dr. Smiley.

 

Dr. Catherine Bollard webinar screen grab

In the News: The challenges of pediatric clinical trials

Dr. Catherine Bollard webinar screen grab“Pediatric cancer is rare, when you compare it to other forms of cancer, especially adult solid tumors. Often pharma companies are not wanting to fund trials that are exclusively to support a pediatric cancer indication. This is a question that I get asked a lot: How to deal with the so-called ‘valley of death’? … You can successfully complete a phase 1/phase 2 trial, show a safety and efficacy signal, but then lack the funds to get FDA approval. Several of us in the field are looking at other strategies to fill this gap, like forming consortiums and using institutional support.”

Catherine Bollard, M.D., M.B.Ch.B, director of the Center for Cancer and Immunology Research, joined Nature to talk about clinical trials for children, including the significant challenges she and her colleagues face to ensure potentially successful treatments have the funding to make it through the approval process. Learn more about her thoughts on the current landscape for pediatric clinical trials and her work on CAR-T cell therapies in her webinar.

Cancer cells

DOD $1.3M award will launch clinical trial to treat sarcoma

Cancer cells

MPNST is a type of cancer called a sarcoma.

The Department of Defense (DOD) awarded Children’s National Hospital $1.3M to launch a unique clinical trial. The trial will evaluate the safety of a novel drug for patients with a rare but aggressive cancer known as malignant peripheral nerve sheath tumors (MPNST).

MPNST is a type of cancer called a sarcoma. While rare in the general population, about half of all MPNST are diagnosed in people with Neurofibromatosis Type 1 (NF1), a condition characterized by changes in skin coloring.

“MPNST is a life-threatening cancer for which there are no adequate medical options,” said AeRang Kim, M.D., Ph.D., director of clinical research of the Division of Oncology at Children’s National. “With the support of this grant, we will conduct a clinical trial to identify effective agents that could be of great benefit to all patients with NF1 who are at risk for sarcoma.”

MPNST are aggressive and frequently metastasize. The tumors that are not able to be removed with surgery rapidly progress and become lethal. In people with NF1, MPNST often develops within benign tumors, especially atypical benign tumors.

The hold-up in the field

Scientists have been looking at the cell signaling process within both pre-cancerous tumors and cancerous MPNST. Previous research has shown that the MEK and MDM2 signaling pathway influence the development and growth of these tumors. By blocking this interplay, the Zhu Laboratory at Children’s National has demonstrated that tumors can get smaller when treated with drugs that inhibit MEK and MDM2 in pre-clinical models.

What’s unique

The trial is uniquely designed to evaluate target inhibition of novel drugs by looking at signals that may help in determining tumor response. This work will provide people with NF1 and MPNST potentially helpful treatments and increase the knowledge for all people with NF1 and those at risk of MPNST. The drugs will be available to all patients who enroll to the study.

histological image of Wilms Tumor

Leading Wilms tumor research nationwide: Q&A with Jeffrey Dome, M.D., Ph.D.

histological image of Wilms Tumor

Children’s National has become a resource for patients and families with Wilms tumor.

During the past year, Children’s National Hospital saw nearly 100 patients with Wilms tumor and other less common kidney cancers of childhood, far more than most centers in the country. This is largely due to the reputation the hospital has established for specializing in these diseases. While most patients with Wilms tumor have excellent outcomes, a significant minority of children with kidney cancer do not fare well. Children’s National has become a resource for patients and families with these challenging cancers.

Behind this reputation is Jeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders and division chief of Oncology at Children’s National, and the team of researchers he leads. For over a decade, he chaired the Children’s Oncology Group Renal Tumor Committee, an opportunity that gave him and his work great exposure.

Dr. Dome shares more on how Children’s National is leading in this space and what the future holds for new, exciting Wilms tumor treatment options.

Q: How is Children’s National leading in this space?

A: The good news is that for the most common type of childhood kidney cancer, Wilms tumor with “favorable histology,” the survival rate is more than 90%, which is an incredible success story. But approximately 25% of children and teens with other types of Wilms tumor and other kidney cancers do not fare as well. We specialize in kidney cancers that are harder to treat, such as anaplastic Wilms tumor, relapsed favorable histology Wilms tumor, bilateral Wilms tumor, clear cell sarcoma of the kidney, malignant rhabdoid tumor and renal cell carcinoma. Because we see a relatively large number of patients, we can draw on our prior experience and observations to recommend the best treatment options.

Q: What’s unique about this research?

A: We have several early-phase clinical trials that are of interest for children with relapsed kidney tumors. Some of these trials are part of research consortia, such as the National Cancer Institute-funded Pediatric Early Phase Clinical Trials Network (PEP-CTN). Other studies have been developed in-house at Children’s National, including a couple of studies using T cells to target pediatric solid tumors. The T cells that have been engineered by the Children’s National Cellular Therapy Laboratory are of particular interest for Wilms tumor because they target a protein called WT1, which is expressed in most Wilms tumors. In fact, WT1 was named after Wilms tumor. We have now had more than 25 patients with relapsed Wilms tumor come from around the country to participate in these studies. Based on early successes, we are continuing this line of research and trying to improve the technology in the current generation of studies.

Dr. Yang of Children's National Research Institute

Unlocking treatments for neuroblastoma

Dr. Yang of Children's National Research Institute

Dr. Jianhua Yang talks about his latest research into neuroblastoma treatments at Children’s National Hospital.

Curing neuroblastomas is going to take years of investigation and persistence, and the team at the Center for Cancer and Immunology Research at Children’s National Hospital is laying the foundation for breakthroughs. Recently, Jianhua Yang, Ph.D., and his colleagues completed a study providing proof-of-concept, preclinical evidence for exploring ulixertinib as a novel pharmaceutical approach for targeting neuroblastomas.

The big picture

This inhibitor blocks a type of communication inside a cell called the extracellular signal-regulated kinases (ERK), which are believed to drive the growth of neuroblastomas and various cancers. In a study of preclinical models published in Cancers, ulixertinib strongly inhibited the proliferation of high-risk neuroblastoma cells inside and outside of living organisms. Investigators also found that ulixertinib sensitized the cancer cells for treatment with the conventional chemotherapy drug, doxorubicin. Yang and his colleagues hope that finding inhibitors like ulixertinib could someday unlock a modality for treating neuroblastomas.

What we hope to discover

“We are trying to figure out if we can find a novel target, which no one has studied,” Yang said. “Some kinases, over-expressed in neuroblastoma and medulloblastoma, are interesting in terms of their expression pattern. We want to learn how they can be activated and promote tumor growth, and then we can develop therapies to safely target that cellular change.”

Neuroblastoma is the most common pediatric extracranial tumor, accounting for 15% of childhood malignancy-related deaths. Although some lower-risk versions of the disease can be cured, high-risk neuroblastomas have proven invulnerable to treatments for decades.

Moving the field forward

Working multiple research tracks, Yang’s lab is also investigating antibody-based immunotherapy that could be used to block the growth of neuroblastomas. Combined with chemotherapies, he and others at Children’s National believe these potential therapies could change the way pediatric cancers are treated and improve the quality of life for survivors.

“It’s like a religion,” Yang said. “You have to believe in yourself. The chance to fail is high, but you have to believe. If we can develop one or two drugs before my retirement, that’s a huge success.”

Dalia Haydar

Harnessing children’s immune systems to fight their own brain tumors

Dalia Haydar, Pharm.D., Ph.D., principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies, recently joined Children’s National Hospital to help develop breakthrough treatments that hopefully will be a key in the fight against pediatric brain tumors. She brings her deep experience at St. Jude Children’s Research Hospital to the Center for Cancer and Immunology Research (CCIR) to help support the NexTGen team’s 10-year, $25-million Cancer Grand Challenges award.

Dalia – literally – has drive: She commutes 180 miles round trip from her home in Hershey, Pa., to her lab. She says she is grateful to be at one of the few research institutions in the world that is researching how to harness the power of CAR T-cell therapies to attack solid tumors in kids. While these therapies have been approved to treat leukemia and other blood cancers, solid tumors have proven far more stubborn. Haydar has tremendous hope that she and the team led by CCIR Director Catherine Bollard, M.D., M.B.Ch.B., will change that.

Q: Could you explain the importance of this research?

A: Unfortunately, once a patient is diagnosed with a brain tumor, especially a kid, there’s very little we can do. Using chemotherapy or radiation therapy has big disadvantages because of developmental delays and other side effects. We are hoping this kind of immunotherapy – where we take the patient’s own immune cells and engineer them in the lab to attack their cancer – will eradicate their very harsh and aggressive tumors, without causing significant adverse effects.

Q: How are researchers at Children’s National going to attack solid tumors with a treatment originally designed for blood cancers?

A: We have a lot of resources and expertise at Children’s National that we are trying to put together to develop a therapy that would cure brain tumors. Unfortunately, solid tumors are hard to treat and there are several challenges for any kind of immunotherapy. But right now, being at a place where all the necessary resources, support and expertise are available, we are hoping to address each of these challenges, and we are determined to do something in a meaningful timeframe to push that survival curve toward the advantage of those kids.

Q: How soon can this work be done?

A: Within two or three years, we are hopeful we’ll be able to identify the best working regimen of this CAR T-cell immunotherapy and investigate if it will work in a patient. I foresee, in the next 5 to 10 years, that we’re hopefully going to have such therapy for kids with brain tumors.

Q: What has surprised most you in your work?

A: There are so many challenges in developing immunotherapies for kids with brain tumors. First, if it works for adults, it doesn’t necessarily work for kids. Some of the tumors in kids are more aggressive. We need to understand the tumor itself, besides understanding the immunotherapy we’re developing.

The other challenge is CAR-T immunotherapy is not like a pill or taking radiotherapy that is standardized for several patients. It’s a very expensive therapy. It’s taking the patient’s own immune cell, like a bone marrow transplant. We put it in the lab, re-engineer the cells without transforming them into a cancer cell, enable those immune cells to attack the cancer, and then put them back into the patient. There are a lot of steps you need to take to make sure you don’t artificially harm those cells or introduce contamination.

One of the most intriguing challenges for me is how we make immunotherapy work for kids who have different kinds of brain tumors – a medulloblastoma versus a glioma versus an embryonal tumor. This is one of the challenges that keeps me on my toes, and I’m hoping to answer.

Q: What is the power of being in a multi-center environment like the Children’s National Research Institute?

A: We have to do enough science on the bench to support any proposal for the therapy to move to the clinic. The last thing we want to do is to investigate a drug or therapy in patients without really knowing how it works and the potential adverse effects. Being able to work with researchers at different stages of the bench-to-bedside spectrum, as well as being able to have access to patient samples and innovative preclinical models, helps push the science forward in a shorter time frame.

Catherine Bollard

In the news: Novel research to stop pediatric brain tumors

“The team is really bringing in very new ideas from mathematical modeling, engineering, all the way to cell therapy, immunotherapy and immunology…This is what really excites and energizes us to be part of this great team, to address the Cancer Grand Challenge, to better target pediatric solid tumors.”

The Cancer Letter connected with Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, for a conversation about her work as a leader of the Cancer Grand Challenges NexTGen team. The $25 million effort is funded by Cancer Research U.K. and the National Institute of Health’s National Cancer Institute and the Mark Foundation for Cancer Research. Its ambitious goal: find novel therapies to break the stalemate in the treatment of pediatric solid brain tumors in the next 10 years. Bollard shared her work plan and the “secret sauce” that gives the team its edge with The Cancer Letter. Find out more about the hope behind this effort in the full interview here.

Catherine Bollard at People V. Cancer summit

In the news: People v. pediatric cancer

“I just want to hammer home the fact that, if you have a child with a pediatric solid tumor who relapses, most likely the chemotherapy that will be treating that child will be the same chemotherapy that a child diagnosed 20 years ago would have received. This is how little progress has been made…. This is what we are trying to change.”

Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, pulled the curtain back on her work fighting pediatric brain tumors at The Atlantic’s People V. Cancer summit. This annual event brings together leading voices from the front lines for in-depth conversations about how to stop this complex and lethal disease. Dr. Bollard discussed the unique importance of collaboration among pediatric oncologists and the optimism she has for using a patient’s immune system to go after solid tumors with CAR T therapies.

Innovations for health equity: Food pharmacy app wins Hackathon

When families come into the endocrinology clinic, 66% of prediabetes and Type 2 diabetes patients screen positive for food insecurity. One remedy: a smartphone app envisioned by Children’s National Hospital researchers to communicate with families between visits and provide resources to help stock pantries with nutritious foods.

The Children’s National Food Pharmacy app is on its way from idea to reality, thanks to the inaugural Health Equity in Research Hackathon event at the Children’s National Research & Innovation Campus. This team-based, “Shark Tank”-like competition involved roughly 50 experts designing creative healthcare solutions that could be delivered through ubiquitous smartphones.

“It takes a village to raise a child, and we want to show that at Children’s National we are part of that community,” said food pharmacy founder and diabetes educator Alexis Richardson, M.S., R.D., L.D.N., C.D.C.E.S.

Why it matters

The rate of new-onset Type 2 diabetes increased by a staggering 182% during the first nine months of the COVID-19 pandemic. Now, the Children’s National food pharmacy provides families that screen positive for food insecurity during quarterly clinic appointments with a 50-pound bag of medically-tailored groceries.

The new app, as envisioned, would follow them home to connect them with food bank information and other nutritional resources, eliminating paper forms and other hurdles that get in the way of care.

What’s ahead

Children’s National leaders are committed to making the proposal a reality. “We are going to support today’s winner through the next steps to prepare them to enter the app development pipeline at the Sheikh Zayed Institute,” said Lisa Guay-Woodford, M.D., director for the Clinical and Translational Science Institute at Children’s National (CTSI-CN) and one of the main judges of the competition.

The app development will happen in the months ahead. Kevin Cleary, Ph.D., technical director of the Sheikh Zayed Institute of Pediatric Surgical Innovation, said the Hackathon planted the seeds. “It really depends on the drive of the individual to see the idea to fruition,” Cleary told competitors.

Other app entries were encouraged to continue their work:

  • The Surgical Checklist, led by Brian K. Reilly, M.D., co-director of the Cochlear Implant Program: this app would help patients and providers successfully navigate the often-confusing pre-operative checklist, including required physical exams, lab work, imaging and pre-procedure fasting. Reilly said the hospital handles about 15,000 cases a year, and about 10% are rescheduled, often for reasons that could be avoided with digital organization and reminders for families.
  • More than Determined, led by Pediatrician Jessica Lazerov, M.D., M.B.A.: this app aims to give time-strapped providers a platform to better understand and address social determinants of health – such as access to safe housing, education and jobs – that can promote better preventative care outcomes.

The Health Equity in Research Hackathon was created by the new Health Equity in Research Unit, a joint initiative between the CTSI-CN and the Center for Translational Research within the Children’s National Research Institute.

Dr. Lisa Guay-Woodford and the winners of the Health Equity in Research Hackathon

Dr. Lisa Guay-Woodford, director for the Clinical and Translational Science Institute, joins the winners of the inaugural Health Equity in Research Hackathon: the Children’s National Food Pharmacy. The team’s proposed app will connect families facing food insecurity with resources and guidance for nutritious eating.

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.

Researchers hope to uncover puzzling mechanism of vision loss in kids with $2.7M DOD award

The Department of Defense Neurofibromatosis Research Program awarded Children’s National Hospital $2.7M to better understand a pediatric tumor as a blinding disease. The study design will specifically focus on targeting immune responses during the development of the tumor as a means to prevent or preserve vision before the tumor-associated irreversible neurological damage.

Why it matters

Nearly 20% of individuals with neurofibromatosis type 1 (NF1) develop tumors along the anterior visual pathway, involving optic nerves, optic chiasm and optic tracts, known as NF1-associated optic pathway gliomas (NF1-OPGs). This tumor is mainly diagnosed in children younger than seven years, which could lead to a lifelong disability.

NF1-OPGs often grow extensively along the optic pathway, and surgery is a high-risk treatment option. Consequently, human tumor tissues are rarely available for research.

Why we’re excited

“We are very excited about this research because, if successful, we will provide a strategy to treat patients with NF1-OPGs before visual impairment becomes irreversible,” said Yuan Zhu, Ph.D., scientific director and Gilbert Family Endowed professor at the Gilbert Family Neurofibromatosis Institute and senior investigator at the Center for Cancer and Immunology Research, both part of Children’s National. “We combine the expertise of glioma at the Children’s National and retinal biology at the NIH/NEI.”

The research will combine the synergistic expertise between Zhu on NF1 and OPG using pre-clinical models and Drs. Han-Yu Shih and Wei Li at the National Eye Institute of the National Institutes of Health (NIH/NEI) on retinal biology and immunology.

What’s unique

To shed light on the chemical signaling that occurs in the optical nerve with the presence of gliomas, the research approach will have three aims:

  • Isolate and characterize this abnormally infiltrating inflammatory cells and perform multi-omics experiments, including sophisticated genomic, epigenomic and transcriptomic assays, to study them during OPG initiation and progression.
  • Prevent or alleviate OPG-associated nerve damage, RGC death and vision loss.
  • Develop a novel model using the newly established genetic system to identify signals that induce inflammatory responses.
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.