Tag Archive for: Cancer

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.”

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.”

Eugene Hwang

Eugene Hwang, M.D., appointed chief of Oncology

Eugene Hwang

Dr. Hwang has been part of the Children’s National team for 13 years and most recently served as the associate chief of Oncology.

Eugene (Gene) Hwang, M.D., has been appointed to the role of chief of Oncology at Children’s National Hospital.

Dr. Hwang has been part of the Children’s National team for 13 years and most recently served as the associate chief of Oncology.

“I joined the division in 2010, fairly new to the job and hoping to simply learn how to treat pediatric cancer. Thirteen years later, I have learned from an almost overwhelming number of people – colleagues, mentors, patients and their families,” Dr. Hwang said. “Our field constantly reminds us of the urgent need for better treatments; in pursuit of that goal, the program at Children’s National has innovated at a level which has taught me the importance of translational and clinical research, connections within our team and the community, and above all, our commitment to our patients. I am honored and excited to help lead this team to continue in their mission to cure more children of their cancer and with fewer side effects.”

Dr. Hwang received his degree in cell and molecular biology from Rice University and a medical degree from Duke University. He completed a pediatrics residency at Brown University/Hasbro Children’s Hospital and returned to Duke for fellowships in pediatric hematology/oncology and pediatric neuro-oncology.

Since Dr. Hwang joined Children’s National in 2010, he has risen to international prominence for his expertise in pediatric brain tumors. Dr. Hwang holds study leadership roles in several research consortia, including the Children’s Oncology Group (COG), Pediatric Brain Tumor Consortium (PBTC), Collaborative Network for Neuro-Oncology Clinical Trials (CONNECT), Pediatric Neuro-Oncology Consortium (PNOC) and the Collaborative Ependymoma Research Network (CERN).

At Children’s National, he serves as principal investigator for two investigator-initiated studies and is the recipient of a Department of Defense IMPACT grant, the collaborative awardee on multiple NIH grants, and numerous foundation grants.  He has served on several of our clinical and scientific committees, such as director of neuro-oncology fellowship program and vice chair of Children’s National Brain Tumor Institute. In addition, Dr. Hwang was recently installed as the inaugural William Seamus Hughes Professor of Neuro-oncology and Immunology.

“The division already has established itself as one of the premier pediatric oncology programs in the world,” Dr. Hwang added. “Being able to offer an even more cutting-edge therapy so that every child treated at Children’s National has the ability to access world-class treatment is a primary goal of our division and I hope to see our team extend its reach of transformative treatments for more children with cancer.”

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.

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.

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.

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.

 

US News Badges

Children’s National named to U.S. News & World Report’s Best Children’s Hospitals Honor Roll

US News BadgesChildren’s National Hospital in Washington, D.C., was ranked No. 5 nationally in the U.S. News & World Report 2022-23 Best Children’s Hospitals annual rankings. This marks the sixth straight year Children’s National has made the list, which ranks the top 10 children’s hospitals nationwide. In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the sixth year in a row.

For the twelfth straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“In any year, it would take an incredible team to earn a number 5 in the nation ranking. This year, our team performed at the very highest levels, all while facing incredible challenges, including the ongoing pandemic, national workforce shortages and enormous stress,” said Kurt Newman, M.D., president and chief executive officer of Children’s National. “I could not be prouder of every member of our organization who maintained a commitment to our mission. Through their resilience, Children’s National continued to provide outstanding care families.”

“Choosing the right hospital for a sick child is a critical decision for many parents,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings spotlight hospitals that excel in specialized 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.

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

The other three specialties ranked among the top 50 were cardiology and heart surgerygastroenterology and gastro-intestinal surgery, and urology.

illustration of the brain

LIFU successfully delivers targeted therapies past the blood-brain barrier

illustration of the brain

LIFU offers doctors the first opportunity to open the blood-brain barrier and treat the entire malignant brain tumor.

Children’s National Hospital will leverage low-intensity focused ultrasound (LIFU) to deliver therapy directly to a child’s high-grade glioma. The approach offers doctors the first opportunity to open the blood-brain barrier and treat the entire malignant brain tumor.

Children’s National will be the first hospital in the U.S. to treat high-grade pediatric brain tumors with LIFU to disrupt the blood-brain barrier. Crossing it has been a major hurdle for effective therapy. The barrier, a network of blood vessels and tissue, prevents harmful substances from reaching the brain but also stops molecular targeted therapy and immunotherapy from getting into the tumor site and staying there.

“LIFU gives us a way to potentially transiently open up the barrier, so we can deliver novel therapy directly to the tumor and improve the likelihood of survival,” said Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National. “It is the greatest breakthrough we’ve potentially had in the past 50 years or more for the management of these tumors. We made great strides in our understanding of molecular genetics and the molecular drivers of tumors, but we have not yet translated that knowledge into better therapies; this may be our most effective mechanism to overcome the barrier.”

In 2020, Children’s National was recognized as the first worldwide Center of Excellence by the Focused Ultrasound Foundation.

Focused ultrasound (FUS) is a non-invasive therapeutic technology with the potential to transform the treatment of many medical disorders by using ultrasonic thermal energy to specifically target tissue deep in the body. The technology can treat without incisions or the need of radiation.

How it works

Doctors at Children’s National will be using LIFU in two different types of procedures:

  • 5-ALA: Doctors will give the patient 5-aminolevulinic acid (5-ALA) with the LIFU treatment. 5-ALA enters rapidly dividing cells and is activated by the ultrasound to a state where it kills the dividing cells of the tumor. The surrounding normal brain cells around the tumor are not dividing, so they do not take up the 5-ALA and are left unharmed after ultrasound therapy.
  • Microbubbles: While receiving different doses of LIFU over a one- to two-hour period, the patient is given “microbubbles,” which are widely used in medical imaging and as carriers for targeted drug delivery. These microbubbles bounce around against the walls like seltzer, opening the blood vessels and transiently opening that space.

Both studies are the first in the world for pediatric gliomas of the brain stem, allowing experts to treat patients 4-6 weeks after radiotherapy. The patient then receives medication orally or intravenously as it passes through the bloodstream. It does not go at high levels anywhere within the brain except where the blood-brain-barrier was opened, allowing oral medication or immune therapies to rush into the tumor.

The launch of this program comes a few months after the hospital successfully performed the first-ever high-intensity focused ultrasound surgery on a pediatric patient with neurofibromatosis.

Watch this video to learn more.

mother and daughter embracing

Understanding end-of-life treatment preferences for adolescents

mother and daughter embracing

FACE-TC effectively increases communication between adolescents with cancer and their families about the patients’ preferences.

Talking about death and dying is taboo. Some families believe it is their role alone to make end-of-life healthcare decisions or they may believe pediatric advance care planning is against their religion.

In a recent trial, Maureen Lyon, Ph.D., a clinical health psychologist at Children’s National Hospital and lead author of the study, analyzed the value of high-quality pediatric advance care planning and how this enabled families to know their adolescents’ end-of-life treatment preferences.

This is the first fully powered randomized controlled trial to focus on adolescents with cancer and their engagement with their families in pediatric advance care planning conversations.

What this means

Some physicians believe it is not their role to discuss the “what ifs.” Others report that they do not have the training or time to do so. As a result, in clinical practice, adolescents living with a serious illness rarely have documented advance care plans. The default is to provide intensive treatments that potentially increase suffering.

“Despite cancer being the leading cause of disease-related death in adolescents, conversations about goals of care and documentation of end-of-life care and treatment preferences for adolescents with cancer are not a routine and standard part of care,” Dr. Lyon said.

Why it matters

Family-centered advance care planning for teens with cancer (FACE-TC) effectively increases communication between adolescents with cancer and their families about the patients’ end-of-life preferences. This meets the first challenge of pediatric advance care planning – knowledge of patient’s preferences.

This low-tech intervention commits to more deeply respecting adolescents with cancer, integrating them into health care decision-making and giving them some control in a low control situation.

The patient and family benefits

“FACE-TC strengthens communication between adolescents with cancer and their families about adolescents’ understanding of their illness, their hopes and fears, their goals of care and their end-of-life treatment preferences,” Dr. Lyon added. “With increased access to palliative care services and pediatric advance care planning, families may better understand that stopping intensive medical interventions when their child is dying is not giving up, but rather choosing how best to spend the final days of one’s life.”

Dr. Lyon and the team at Children’s National have pioneered this effort to give seriously ill adolescents a voice and help families break the ice so they know what their child would want if the worst were to happen. The team also aims to provide an extra level of support for busy clinicians so the first conversation about goals of end-of-life care does not happen in the intensive care unit.

You can read the full trial, An Intervention in Congruence for End-of-Life Treatment Preference: A Randomized Trial, in Pediatrics.

You can also read the last manuscript from this clinical trial, Effect of the Family-Centered Advance Care Planning for Teens with Cancer Intervention on Sustainability of Congruence About End-of-Life Treatment Preferences, in JAMA Network.

illustration of brain tumor

International initiative aims to find rare brain tumor treatments

illustration of brain tumor

Rare brain tumors are not as well characterized due to the paucity of biological and clinical data available.

Certain brain tumors can be hard to diagnose. And as such, that makes it complicated to find a treatment.

In an effort to identify and tailor treatments to patients with rare brain tumors, Children’s National is launching a rare brain tumor initiative. The hospital is collaborating with other hospitals in North America, South America and Europe to compile a registry of children diagnosed with rare brain tumors. The registry will collect biospecimens, clinical and radiological data from patients diagnosed with certain rare brain tumors.

The goal is to find a correlation between the molecular findings and the clinical findings to categorize them. This will help doctors get different prognosticators or different treatment approaches.

Here, Adriana Fonseca Sheridan, M.D., pediatric neuro-oncologist at Children’s National Hospital, tells us more about this international initiative.

What’s been the hold-up in the field?

The recent incorporation of molecular features as part of the diagnostic criteria and classification of brain tumors highlighted a high biological and molecular heterogeneity within previously histologically defined entities. The improvement in our diagnostic capabilities have been incredibly useful to stratify patients into different disease-specific risk groups and tailor therapeutic approaches accordingly in the most common brain tumors. In contrast, rare brain tumors are not as well characterized due to the paucity of biological and clinical data available. Additionally, newly molecularly defined entities lack specific clinical and therapeutic data and represent a major challenge to patients and doctors alike.

How does this work move the field forward?

The overarching objective of the international rare brain tumor registry is to deepen our understanding of the biological underpinnings of rare brain tumors. The registry also seeks to create infrastructure that allows for development of rational and personalized treatment strategies for children with rare entities.

What are you hoping to discover?

We hope to characterize the clinicopathological features and identify risk factors for survival and optimal therapeutic approaches of:

  • CNS sarcomas
  • BCOR-ITD tumors
  • Astroblastoma/MN1 altered tumors
  • Histologically ambiguous/unclassifiable brain tumors

How unique is this work?

Children’s National will spearhead the development of this initiative and lead an effort to prospectively collect biological specimens, radiological and clinical data that allow us to better understand the biologic mechanisms and therapeutic susceptibilities of these rare diseases.

We know that the best way to lead the advancement of the field in rare diseases is through collaboration. Therefore, we will synchronize efforts and collaborate with our European colleagues. They will be running a similar initiative. Our goal is to generate meaningful and robust data that will allow us to better understand how to successfully treat patients with these rare brain tumors across the globe.

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.

doctor and cancer patient smiling

Manufactured leukemia-specific T cells may help increase survival rates

doctor and cancer patient smiling

Infusion of a novel, multi-targeted donor-derived T-cell therapy is safe and well-tolerated in patients with high-risk or relapsed leukemia after a donated bone marrow transplant, according to a new study published in Blood Advances.

Infusion of a novel, multi-targeted donor-derived T-cell therapy is safe and well-tolerated in patients with high-risk or relapsed leukemia after a donated bone marrow transplant, according to a new study published in Blood Advances. The findings suggest that this strategy may make a difference in these patients, as will be evaluated in later phase trials.

“A tumor cell is very clever because it tries to hide from T-cell therapies by deleting or down regulating targets that the T cell is directed towards,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital and co-senior author. “This novel cell therapy has the potential to get around that escape by targeting multiple proteins in a single product, making it much harder for the cancer cell to hide from the immune attack by the T cells.”

The tumor-associated antigen-specific T cell (TAA-T) product targets WT1, survivin and PRAME, which are proteins that play a role in cancer cell proliferation and survival. They are overexpressed in leukemia and many other human malignancies. The researchers chose to expand the T cells to target many malignancies through at least one expressed antigen. The manufactured TAA-T products are derived from peripheral blood mononuclear cells (PBMCs) obtained from the patient’s own BMT donor.

The hold-up in the field

Conventional therapies for patients with high-risk or relapsed malignancies often fail due to toxicity associated with additional chemotherapy and second transplant, particularly in those who relapse early after transplant. This novel cellular immunotherapy approach is shown to be safe and targets antigens that are found in CD19 positive and negative blood cancers, which may broaden the applicability to other cancer types, such as acute myeloid leukemia, that are currently lacking effective T cell therapy options.

What’s next

“Evaluation and tracking of unique T cell receptor clonotypes in patients following TAA-T cell infusion demonstrated expansion and persistence of some clonotypes up to 6 months to one-year post-infusion,” said Hannah Kinoshita, M.D., oncology fellow at Children’s National and co-lead author. “In future studies, we are hoping to identify and track unique target antigen-specific clonotypes from the T cell product infused to better understand the immunobiological effect of the infused T cells and how that can be translated into improved clinical outcomes.”

Children’s National Hospital leads the way

The Cell Enhancement and Technologies for Immunotherapy (CETI) program at Children’s National specializes in developing and analyzing novel cellular therapeutics such as this one.

You can read the full study “Outcome of Donor-derived TAA-T cell therapy in Patients with High-risk or Relapsed Acute Leukemia Post Allogeneic BMT,” in Blood Advances. Children’s National researchers worked in partnership with Rick Jones, M.D., co-senior author and Kenneth Cooke, M.D., Ph.D., co-lead author, both at Johns Hopkins Medicine.

Illustration of white blood cells attacking a cancer cell

Alpha/beta T cell depletion lifts barriers to transplantation

Illustration of white blood cells attacking a cancer cell

Removal of A/B T cells from the infused cell product significantly minimizes the risk of GvHD and eliminates the need for immunosuppressive medications after transplant.

Alpha/beta T cell depletion (A/B TCD) is a cutting-edge hematopoietic stem cell transplant (HSCT) technique by which donor derived immune cells, called A/B T cells, can be removed by selectively using magnetic beads before the donor cells are infused into the recipient’s body. A/B T cells have the potential to cause life threatening inflammation in the recipient’s body, called graft-versus-host disease (GVHD). GVHD is a major complication after transplant, especially when the donor is not fully matched. Therefore, removal of A/B T cells from the infused cell product (graft) significantly minimizes the risk of GVHD and eliminates the need for immunosuppressive medications after transplant.

Unlike previous methodologies that completely remove all immune cells, the novel A/B TCD approach preserves beneficial immune cells (like gamma delta T cells, natural killer cells, monocytes and dendritic cells) in the graft to preserve the capability to fight viral infections and residual cancer. Therefore, this innovative transplant approach can cure leukemia while decreasing the risk of life threatening infections and relapse after transplant.

In this Q&A, Anant Vatsayan, M.D., blood and marrow transplant specialist at Children’s National Hospital, tells us more about this new exciting technique.

Q: What is the specific research question that you are hoping to answer?

A: Children’s National Hospital is participating in the largest multicenter pediatric trial of A/B TCD hematopoietic stem cell transplant in the United States. The primary objective of this research is to assess whether disease-free survival at one-year after-HCT for children with high-risk leukemia and myelodysplastic syndrome can be improved with A/B TCD hematopoietic stem cell transplant.

Patients with other types of blood disorders may also be eligible to undergo A/B TCD hematopoietic stem cell transplant in this study based on the discretion of the principal investigator. The study will also assess the overall survival and rates of acute and chronic GVHD. Another objective is to compare the cost of transplantation using half-matched (haploidentical) donors versus other stem cell sources (for example, matched unrelated adult donors or cord blood donors) at participating centers.

Q: Why is this work exciting?

A: A/B TCD hematopoietic stem cell transplant has several benefits:

  • One of the remarkable benefits of this technique is the possibility of using haploidentical related donors for transplant if a fully matched related or unrelated donor is not available. This is a common scenario for patients of certain races (African American) and ethnicities (Hispanic) where it is difficult to identify a fully matched unrelated donor. Therefore, A/B TCD hematopoietic stem cell transplant expands the pool of donor options and ensures more equitable donor availability across every race and ethnicity.
  • A/B TCD significantly decreases the risk of severe GVHD and post-transplant infections. It eliminates the need for post-transplant immunosuppressive medications (like cyclosporine, tacrolimus or sirolimus) that can have numerous side effects and require frequent monitoring of drug levels in the blood.
  • The A/B TCD technique also promotes faster recovery of blood counts (engraftment) after transplant. Therefore, patients take fewer medications, have shorter durations of hospitalization for transplant and need less frequent blood tests and clinic visits after transplant. Hence, this patient friendly and family centric transplantation strategy will ensure that patients can spend more time with their family and have a better quality of life.

Q: How do you hope this will benefit patients?

A: Alpha/beta T cell depleted HSCT using half matched (haploidentical) donors will ensure donor availability for almost every patient regardless of race/ethnicity and probability of finding a matched related/unrelated donor. This methodology has tremendous prospects for wider applications, including the use of matched related and unrelated donors with the intent to eliminate the need for post-transplant immunosuppressive medications. This could be especially beneficial for patients with Fanconi anemia or other patients who are at risk of developing severe side effects from the use of immunosuppressive medications.

Q: How unique is this work?

A: The Shirley and William Howard Cellular Therapy Laboratory Stem Cell Processing program processes stem cells and performs cutting edge clinical trials while providing innovative care for patients. This work benefits from access to CliniMACS Plus Cell Selection Device, along with a multidisciplinary team with laboratory and clinical expertise to perform A/B TCD hematopoietic stem cell transplant. Access to our state of the art Cellular Therapy Laboratory allows us to further complement this transplantation strategy with other cellular therapies after transplant, such as virus specific and leukemia targeting T cells, which further mitigate the risk of post-transplant viral infections and leukemia relapse.

cancer cells

Advancing immunotherapy for pediatric brain tumors

cancer cells

While immunotherapy has revolutionized cancer treatments, its efficacy remains relatively undefined in pediatric settings for brain tumors.

While immunotherapy has revolutionized cancer treatments, its efficacy remains relatively undefined in pediatric settings for brain tumors. Children’s National Hospital experts and other institutions argue in a review published in Nature Cancer that there is a need for closer collaborations between academia, industry partners, regulatory bodies and funders to progress the field.

Eugene Hwang, M.D., associate division chief of Oncology and neuro-oncologist at Children’s National, led the review that outlines immunotherapeutic hurdles and simultaneously proposes next steps for immunotherapy use in these patients. These considerations will aid pediatric oncologists make better recommendations and advances in this type of treatment.

“The promise of immunotherapy in helping to cure children with brain tumors is exciting,” Dr. Hwang said. “This type of approach has already revolutionized treatments for many different kinds of cancer, and a comprehensive review of this complicated arena, especially by leading voices in the field, can help set the stage for finally moving the needle for these patients.”

The review is especially helpful as children harbor unique elements of immunity and the brain presents distinct obstacles to immune attack that are not present in other cancers. For example, there are challenges in antigen identification, the blood-brain barrier and the tumor microenvironment. For many pediatric cancer doctors as well this novel, complex form of therapy is outside of their historical training.

To overcome these challenges, the authors encourage philanthropic organizations and patient advocacy groups to be part of the process that can help fill funding gaps in patient-focused pre-clinical and clinical research and educate patients and families.

“Multiple stakeholders around pediatric brain cancer immunotherapy must be mobilized in a concerted fashion,” Hawk et al. argue in the piece. “The need for close academic collaboration with industry partners and regulatory bodies is increasingly apparent given the unique pediatric phenotypes and complex outcomes in immunotherapeutic trials, and progress will be made at the interface of the interactions of all these key stakeholders.”

The group of internationally renowned pediatric brain tumor-focused immunotherapy experts comprehensively reviewed the advances in the major modalities of immunotherapy and the landscape of preclinical modeling for these patients to date.

Investigators at Children’s National, for example, are leading several national and international trials involving immunotherapy which have spurred international meetings with a focus in childhood brain tumor immunotherapies.

“The multiple T cell trials led by Children’s National are perfect examples of truly field-leading innovative immunotherapy, as are the other trials that are led by our own investigators,” Dr. Hwang added.

Dr. Javad Nazarian

Q&A with Dr. Javad Nazarian on his upcoming work on low-grade gliomas

Dr. Javad Nazarian

Supported by the Gilbert Family Foundation, Dr. Nazarian’s return is part of a special research program within the Gilbert Family Neurofibromatosis Institute that focuses on NF1 research.

Javad Nazarian, Ph.D., M.Sc., associate professor of Pediatrics at George Washington University and professor at the University of Zurich, has expanded his research group at Children’s National to focus on Neurofibromatosis type 1 (NF1) transformed low-grade gliomas (LGGs). Dr. Nazarian will apply his expertise from establishing a successful DIPG (diffuse intrinsic pontine glioma) and DMG (diffuse midline glioma) program in Zurich Switzerland and previously at Children’s National.

In addition to his continued research in Zurich, as a principal investigator at the Department of Genomics and Precision Medicine at Children’s National Dr. Nazarian plans on aggregating his knowledge to the new research and work spearheaded at Children’s National. As one of the first research teams to move to the Children’s National Research & Innovation Campus, Dr. Nazarian’s group is excited to use the opportunity to establish cutting-edge and clinically translational platforms.

Supported by the Gilbert Family Foundation, Dr. Nazarian’s return is part of a special research program within the Gilbert Family Neurofibromatosis Institute that focuses on NF1 research. This research includes associated gliomas with a special emphasis on NF1-associated transformed anaplastic LGGs. His team will develop new avenues of research into childhood and young adult NF-associated LGGs with a special emphasis on transformed high-grade gliomas.

Dr. Nazarian is excited for what’s to come and his goals are clear and set. Here, Dr. Nazarian tells us more about his main objectives and what it means for the future of pediatric neuro-oncology care at Children’s National.

  1. What excites you most about being back at Children’s National?

I have received most of my training at Children’s National, so this is home for me. Being one of the nation’s top children’s hospitals gives a unique advantage and ability to advocate for childhood diseases and cancers. It is always exciting to play a part in the vision of Children’s National.

  1. What are some of the lessons learned during your time working in Zurich? And how do you think these will compliment your work at Children’s National?

We developed a focused group with basic research activities intertwined with clinical needs.  The result was the launch of two clinical trials. I also helped in developing the Diffuse Midline Glioma-Adaptive Combinatory Trial (DMG-ACT) working group that spans across the world with over 18-member institutions that will help to design the next generation clinical trials. I will continue leading the research component of these efforts, which will have a positive impact on our research activities at Children’s National.

  1. How does your work focusing on low-grade gliomas formulating into high-grade gliomas expand and place Children’s National as a leader in the field?

Scientifically speaking, transformed LLGs are very intriguing. I became interested in the field because these tumors share molecular signatures similar to high-grade gliomas (HGGs). Our team has done a great job at Children’s National to develop tools – including biorepositories, avatar models, drug screening platforms, focused working groups, etc. – for HGGs. We will apply the same model to transformed LGGs with the goal of developing biology-derived clinical therapeutics for this patient population.

  1. How will this work support families and patients seeking specific neuro-oncology care?

We will develop new and high thruput tools so that we can better study cancer formation or transformation. These tools and platforms will allow us to screen candidate drugs that will be clinically effective. The main focus is to accelerate discovery, push drugs to the clinic, feed information back to the lab from clinical and subsequently design better therapies.

  1. You are one of the first scientists to move to the Children’s National Research & Innovation Campus. What are some of the valuable changes or advancements you hope to see as a result of the move?

The campus will provide high-end facilities, including cutting-edge preclinical space, and allow for team expansion. The close proximity to Virginia Tech will also provide an environment for cross-discipline interactions.

  1. Anything else you think peers in your field should know about you, the field or our program?

The team at Children’s National includes Drs. Roger Packer and Miriam Bornhorst. Both have provided constant clinical support, innovation and clinical translation of our findings. I look forward to working with them.

Jeffrey Dome

Q&A with Dr. Jeffrey Dome on his new role as Continental President of SIOP-North America

Jeffrey Dome

In March 2021, Jeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, was elected as the International Society of Paediatric Oncology’s (SIOP) Continental President of North America.

In March 2021, Jeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, was elected as the International Society of Paediatric Oncology’s (SIOP) Continental President of North America.

On October 21-24, the society will hold its 53rd SIOP Annual Congress virtually. During the congress, Dr. Dome will begin his 3-year term as SIOP continental president of North America and will also chair and speak at an educational symposium on current approaches to the treatment of recurrent Wilms tumor.

Dr. Dome attended his very first SIOP meeting in 2005 and was captivated by how regional context influences pediatric cancer treatment. In 2017, he was chair of the local organizing committee for the 49th annual congress in Washington, D.C., and served on the SIOP Board of Directors.  After 15 years of involvement and attending many of the annual meetings, Dr. Dome shares what he looks forward to while serving as continental president of SIOP North America and the legacy he hopes to leave behind.

  1. What does it mean to you to be elected SIOP continental president of North America?

I’m very excited about this role. There are several important societies and organizations in North America that have made a mark on the field of pediatric oncology, but SIOP is unique in its sole focus on childhood cancer and global approach to improving outcomes, as encapsulated by its vision statement: No child should die of cancer: cure for more, care for all.

  1. What excites you most about this role?

In an eye-opening statistic, North America has only about 10% of the global burden of childhood cancer and less than 2% of worldwide childhood cancer deaths.  Although we relentlessly strive to improve childhood cancer outcomes in the United States, what we experience here is just the tip of the iceberg of the worldwide problem. SIOP seeks to make a difference on the international level by improving education, research and access to care for children with cancer around the world. And I’m excited to have a platform to lead North American ambassadors to do that.

Even though North America has a relatively small fraction of the overall childhood cancer cases, we are one of the most well-resourced continents. The question is, how can we use our knowledge, technology and resources to help the rest of the world.  A big part of this role is to make connections and liaisons to move the needle on improving outcomes.

The other thing we’ve learned from a research standpoint is that pediatric cancers are relatively uncommon and are becoming even rarer through molecular classification, which divides cancers into small genetically defined subgroups.  While these advances are tremendously exciting, they require international collaboration to amass a sufficient number of patients to evaluate novel treatment strategies.  My vision for SIOP North America is to be a convener of researchers and connect people around the world to facilitate that work.

  1. What are some of your goals while serving as continental president?

We recently sent a survey to more than 450 SIOP North America members and had a nearly 45% response rate, which I’m told is superb.  This speaks to an excellent level of engagement in SIOP’s mission, with many members volunteering to participate in committees related to research, advocacy and global health. The majority of the respondents to the survey were physicians but improving childhood cancer treatment takes a holistic approach.  One of my main goals is to increase SIOP North American membership to grow the number of nurses, pharmacists, scientists, psychologists, other behavioral health specialists and clinical research coordinators onboard.

I’d like to also identify two to three very specific projects that will impact pediatric cancer care on a global level. There are different ways to do that. We could improve education in different areas around the world (nursing education that we provide to areas that are lacking nursing support, for example). It could be research education and database education for regions of the world that would like to develop more robust research programs. It can also be medical support and developing medical guidelines for oncologists around the world that are adjusted to different levels of resources that are available.

The other goal would be to enhance supportive care and education for cancer care delivery on the global level.

  1. Why is this work important for you?

One of my mentors from when I was a junior faculty member advised me that to be a well-rounded oncologist, one must be familiar with how childhood cancer is treated around the world because different regions have different approaches. There is something to be learned from everyone.  I took that advice to heart and have tried to look beyond the North American approaches.  I think it’s very important to have a global exchange of ideas and serving as continental president of SIOP-North America will enable more to facilitate this dialogue.

  1. What’s the legacy or impact you hope to leave behind?

SIOP North America has a strong and devoted membership but has largely functioned at the level of the individual members.  I hope to bring more structure to the organization to tackle the global challenges of childhood cancer treatment.

Once this structure is in place, I hope to complete two or three SIOP-North America initiatives that have a measurable impact on improving childhood cancer care delivery or outcomes.  The specific projects have yet to be defined but will likely be in the categories of enhancing education, supportive care and facilitating research infrastructure. There’s so much to tackle that if you just look at the overall problem of childhood cancer, it’s overwhelming.  We’re not going to be able to solve everything in three years, but if we could have a few victories and be able to move the needle in some areas, I think that would be a huge success.