Wilm's Tumor

PRAME-specific T cell product may facilitate rapid treatment in cancer settings

Wilm's Tumor

PRAME is a cancer-testis antigen that plays a role in cancer cell proliferation and survival and is overexpressed in many human malignancies, including Wilms tumor. “Wilm’s Tumor (Nephroblastoma)” by euthman is licensed under CC BY 2.0.

Generated preferentially expressed antigen in melanoma (PRAME)-specific T cells from healthy donors can kill PRAME-expressing tumor cells in vitro, researchers at Children’s National Hospital found. Several novel epitopes, which are antigens that are recognized by the immune system, were also identified for enhanced matching, making this a potential therapeutic option for a broader patient group, according to a study published in Cytotherapy.

PRAME is a cancer-testis antigen that plays a role in cancer cell proliferation and survival and is overexpressed in many human malignancies, including melanoma, leukemia, sarcoma, renal cell cancer and Wilms tumor. PRAME also acts as a foreign substance in the body that can trigger the immune system by activating T cells, making it a good target for anticancer immunotherapy — especially for immunocompromised patients.

“The development of an effective off-the-shelf adoptive T-cell therapy for patients with relapsed or refractory cancers expressing PRAME antigen requires the identification of epitopes essential to the adaptive immune response, which are presented by major histocompatibility complex (MHC) class I and II, and are then recognized by the manufactured PRAME-specific T cell product,” said Amy Hont, M.D., oncologist for the Center for Cancer and Immunology Research at Children’s National Hospital. “We, therefore, set out to extend the repertoire of HLA-restricted PRAME peptide epitopes beyond the few already characterized and demonstrate the cytotoxic activity of PRAME-specific T cells to tumor cells known to express PRAME.”

Immunotherapy options for pediatric patients with high-risk malignancies, especially solid tumors, are few. Tumor-associated antigen-specific T cells (TAA-T) offer a therapeutic option for these patients, and Children’s National is building upon the success of the ongoing clinical trials to optimize this therapy and improve the treatment of our patients.

“These findings will also benefit patients because it better informs the pre-clinical studies of third party TAA-T to treat high-risk malignancies, so that we can move more quickly and safely to clinical trials,” said Dr. Hont.

Stanojevic et al. describes that the T-cell products killed partially HLA-matched tumors, and that this enhanced disintegration of tumor cells compared with non-specific T cells suggests an anti-tumor potential for a clinical trial evaluation to determine the safety and efficacy. Further research about the PRAME-specific T cells will help inform a treatment alternative for patients with solid tumors in the future.

The researchers generated a PRAME-specific T cell bank from healthy donor cells and demonstrated anti-tumor cytolytic activity against tumor lines partially HLA-matched to the T cells and known to express PRAME. By using epitope mapping, they identified several novel epitopes restricted to MHC class I or MHC class II to further inform HLA matching.

“Defining PRAME-specific T cells beyond HLA epitopes could be useful when developing T-cell therapies for worldwide application,” Stanojevic et al. write. “Moreover, creating off-the-shelf products has many potential advantages since such products are readily available for the treatment of patients with aggressive disease or patients for whom an autologous product cannot be manufactured.”

Additional authors from Children’s National are Maja Stanojevic, M.D., Ashley Geiger, M.S., Samuel O’Brien, Robert Ulrey, M.S., Melanie Grant, Ph.D., Anushree Datar, M.S., Ping-Hsien Lee, Ph.D., Haili Lang, M.D., Conrad R.Y. Cruz, M.D., Ph.D.,  Patrick J. Hanley, Ph.D., A. John Barrett, M.D, Michael D. Keller, M.D., and Catherine M. Bollard, M.D., M.B.Ch.B.

Sickle-Cell-Blood-Cells

Treating neurocognitive difficulties in children with sickle cell disease

Sickle-Cell-Blood-Cells

An adaptive cognitive training program could help treat attention and working memory difficulties in children with sickle cell disease (SCD), a new study published in the of Journal of Pediatric Psychology shows.

An adaptive cognitive training program could help treat attention and working memory difficulties in children with sickle cell disease (SCD), a new study published in the of Journal of Pediatric Psychology shows.

These neurocognitive difficulties have practical implications for the 100,000 individuals in the U.S. with SCD, as 20-40% of youth with SCD repeat a grade in school and fewer than half of adults with SCD are employed. Interventions to prevent and treat neurocognitive difficulties caused by SCD have the potential to significantly improve academic outcomes, vocational attainment and quality of life.

The study, led by Steven Hardy, Ph.D., director of Psychology and Patient Care Services at the Center for Cancer and Blood Disorders at Children’s National Hospital, examined a promising approach using an adaptive cognitive training program (known as Cogmed Working Memory Training) that patients complete at home on an iPad.

Using a randomized controlled trial design, children were asked to complete Cogmed training sessions 3 to 5 times per week for about 30 minutes at a time until they completed 25 sessions. The Cogmed program involves game-like working memory exercises that adapt to the user’s performance, gradually becoming more challenging over time as performance improves. The team found that patients with sickle cell disease (SCD) who completed the cognitive training intervention showed significant improvement in visual working memory compared to a waitlist group that used Cogmed after the waiting period. Treatment effects were especially notable for patients who completed a training “dose” of 10 sessions.

“Patients who completed at least 10 cognitive training sessions showed improved visual working memory, verbal short-term memory and math fluency,” Dr. Hardy said.

SCD increases risk for neurocognitive difficulties because of cerebrovascular complications (such as overt strokes and silent cerebral infarcts) and underlying disease characteristics (such as chronic anemia). Neurocognitive effects of SCD most commonly involve problems with attention, working memory and other executive functions.

“This study demonstrates that digital working memory training is an effective approach to treating neurocognitive deficits in youth with sickle cell disease,” Dr. Hardy added. “We also found that benefits of the training extend to tasks that involve short-term verbal memory and math performance when patients are able to stick with the program and complete at least 10 training sessions. These benefits could have a real impact on daily living, making it easier to remember and follow directions in school and at home, organize tasks or solve math problems that require remembering information for short periods of time.”

To date, there have been few efforts to test interventions that address the neurocognitive issues experienced by many individuals with SCD. These findings show that abilities are modifiable and that a non-pharmacological treatment exists.

The Comprehensive Sickle Cell Disease Program at Children’s National is a leader in pediatric SCD research and clinical innovation. This study was funded by a grant from the Doris Duke Charitable Foundation, which was the only Innovations in Clinical Research Award ever awarded to a psychologist (out of 31 grants totaling over $15 million), since the award established a focus on sickle cell disease in 2009.

Novel cancer vaccine targets oncogenes known to evade immunity in melanoma and neuroblastoma models

"Neuroblastoma of the Adrenal Gland (2)" by euthman is licensed under CC BY 2.0

Neuroblastoma of the Adrenal Gland (2)” by euthman is licensed under CC BY 2.0.

A personalized tumor cell vaccine strategy targeting Myc oncogenes combined with checkpoint therapy creates an effective immune response that bypasses antigen selection and immune privilege, according to a pre-clinical study for neuroblastoma and melanoma. The neuroblastoma model showed a 75% cure with long-term survival, researchers at Children’s National Hospital found.

Myc is a family of regulator genes and proto-oncogenes that help manage cell growth and differentiation in the body. When Myc mutates to an oncogene, it can promote cancer cell growth. The Myc oncogenes are deregulated in 70% of all human cancers.

Myc mutations, like the amplification of c-MYC and MYCN, are associated with host immune suppression in melanoma and neuroblastoma tumors, according to the study published in The Journal for Immunotherapy of Cancer.

“Paradoxically, from an immunotherapeutic perspective, a lack of an immune response may offer an opportunity to target those tumors [melanoma and neuroblastoma] that would be less resistant to host immunity assuming potent cellular immunity can be generated against the tumor,” said the authors.

The findings suggest that small molecule inhibitors — I-BET726 and JQ1 — suppress Myc’s uncontrolled cellular proliferation and enhance the immune response against tumor cells themselves, enabling their use as a tumor cell vaccine. The combination of cell vaccine and available therapies that keep the immune responses in check, also known as checkpoint inhibitor therapy, can help inform a personalized therapeutic tumor vaccine in the future.

“The work is pre-clinical and although we have seen excellent responses in these models, we need to determine whether this will also be effective in humans,” said Xiaofang Wu, staff scientist III at Sheikh Zayed Institute for Pediatric Surgical Innovation and lead author.  “For this purpose we have started laboratory testing in human cells. Our eventual hope is to translate these basic science findings to clinical application.”

There is a need for more effective therapies for neuroblastoma and melanoma, given the poor outcome of patients experiencing high-risk or advanced disease through traditional chemotherapy methods.  While the field has developed tumor vaccines and immune-based therapies, c-MYC and MYCN seem to protect the tumor against an immune response, so they often evade cure.

The researchers cautioned that both models induced potent immunity but draw different results, which means that this novel therapeutic vaccine is more effective in the neuroblastoma model than in the melanoma model. The neuroblastoma model resulted in a remarkable 75% cure and significantly improved long-term survival despite a larger initial tumor challenge.

“In contrast, the melanoma tumor gained adaptive resistance that is associated with an imbalance between tumor cell growth and cytotoxic killing and thus the vaccine failed to eradicate the tumor,” said the authors. “Despite potent immune effects from the vaccine, other immunosuppressive molecules will need to be targeted to see the full effects of the vaccine protocol in the melanoma model.”

The study proposes a framework that could be translated for therapeutic patient-specific vaccines for MYCN-amplified neuroblastoma tumors resistant to available therapies.

To understand the exact role of c-Myc and MYCN amplification and their association with immune suppression, the researchers examined 21 human neuroblastoma samples — the majority with metastatic disease — and 324 melanoma samples where only 30 were categorized as MYC amplified. Based on the oncogene’s capability to suppress the immune response, the researchers combined checkpoint inhibitors with pharmacologic molecules — I-BET726 and JQ1 — to target Myc oncogenes in mouse neuroblastoma and melanoma models. They also tested for the effects of different doses, drug combinations and incubation times on tumor cell proliferation, differentiation and gene alteration.

Authors on the study from Children’s National Hospital include: Xiaofang Wu, Ph.D., Marie Nelson, M.D., Mousumi Basu, Priya Srinivasan, Ph.D., Christopher Lazarski, Ph.D., and Anthony Sandler, M.D.

SIOP logo

Jeffrey Dome, M.D., elected SIOP Continental President of North America

Jeffrey Dome

“I’m honored to have been elected as president of a society that is a leader in propelling treatment and advocacy for childhood cancer,” Dr. Dome said. “I look forward to working alongside peers who are committed to efforts to improve outcomes for children with cancer globally.”

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

“I’m honored to have been elected as president of a society that is a leader in propelling treatment and advocacy for childhood cancer,” Dr. Dome said. “I look forward to working alongside peers who are committed to efforts to improve outcomes for children with cancer globally.”

SIOP is the only global multidisciplinary society devoted to pediatric and adolescent cancer. With over 2,600 members worldwide – including doctors, nurses, other health-care professionals, scientists and researchers – the society is dedicated to increasing knowledge about all aspects of childhood cancer.

SIOP will officially welcome Dr. Dome to the position at its Annual Business Meeting in October.

light micrograph of wilms tumor

Evolution of risk stratification for Wilms tumor

light micrograph of wilms tumor

Light micrograph of Wilms tumor.

Wilms tumor is a rare kidney cancer that primarily affects children. Also known as nephroblastoma, it is the most common malignant renal tumor in children. Advances in the treatment of Wilms tumor are some of the great achievements in the field of oncology, improving survival to 90% and decreasing the burden of therapy.

A key factor in the success of Wilms tumor treatment has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient’s risk of relapse. In a review article in Current Opinion in Pediatrics, Jeffrey Dome, M.D., Ph.D., vice president of the Center for Cancer and Blood Disorders at Children’s National Hospital, Marie V. Nelson, M.D., assistant professor of pediatrics in the Division of Oncology, and their colleagues look at the evolution of clinical and biological factors that have been adopted for Wilms tumor.

The authors found that the original National Wilms Tumor Study Group (NWTSG) and International Society of Pediatric Oncology (SIOP) studies relied solely on tumor stage to define treatment. Over time, however, additional factors were incorporated into the risk stratification schema, allowing for a multifactorial precision medicine approach.

The authors conclude that “the application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.”

Read the full study in Current Opinion in Pediatrics.

t-cells attacking cancer cell

Children’s National spin-out cell therapy company receives funding

t-cells attacking cancer cell

Ongoing efforts by researchers at Children’s National Hospital to improve T-cell therapies have led to a spin-out company MANA Therapeutics which has announced a $35 million Series A financing. MANA is a clinical stage company creating nonengineered, allogeneic and off-the-shelf cell therapies that target multiple cancer antigens. Its EDIFY™ platform aims to educate T-cells that target multiple target multiple cell surface and intracellular tumor-associated antigens across a broad range of liquid and solid tumors, with an initial focus on relapsed acute myeloid leukemia (AML).

MANA was founded in 2017, and was based on the research and human proof-of-concept clinical trials conducted by Catherine Bollard, M.D., M.B.Ch.B., Conrad Russell Y. Cruz, M.D., Ph.D., Patrick Hanley, Ph.D. and other investigators at Children’s National along with their colleagues at Johns Hopkins Medical Center. The trials demonstrated safety and anti-tumor activity of MANA’s approach, and Children’s National provided an exclusive license to MANA to further develop this promising technology into commercial products in the field of immuno-oncology.

MANA Therapeutics recruited an experienced leadership team from industry including Martin B. Silverstein, M.D., president and CEO, who is a former senior executive at Gilead Sciences when they acquired Kite Pharma, one of the leading cell therapy companies, as well as Madhusudan V. Peshwa, Ph.D., chief technology officer, who joined from GE Health Care where he had been Chief Technology Officer and Global Head of R&D for Cell and Gene Therapies.

“MANA is building upon the strong foundational science established at Children’s National with a unique approach that promises to produce off-the-shelf allogeneic therapies that do not compromise on safety or efficacy,” said Marc Cohen, co-founder and executive chairman of MANA Therapeutics. “I look forward to continuing to support the MANA team as they advance their internal pipeline for the treatment of AML and select solid tumors, and expand the potential of EDIFY through strategic partnerships focused on new target antigens and cancer types.”

An international leader in the immunotherapy field, Dr. Bollard was an early believer in the potential of immune cell therapies to dramatically improve the treatment of patients with cancer and patients with life-threatening viral infections. Recently, she and her team at the Children’s National Center for Cancer and Immunology Research published findings in Blood showing T-cells taken from the blood of people who recovered from a COVID-19 infection can be successfully multiplied in the lab and maintain the ability to effectively target proteins that are key to the virus’s function.

“Over the past decade we have seen tremendous progress in cancer research and treatment and are beginning to unlock the potential of cell therapy for a variety of tumor types,” said Dr. Bollard. “The human proof-of-concept trials conducted by my team and colleagues showed potential for a nonengineered approach to educating T-cells to attack multiple tumor antigens, which MANA is expanding even further through refinement of the manufacturing process for an allogeneic product and application to a broader set of antigens in a variety of clinical indications and settings.”

Read more about how the Series A funding will enable rapid progress with MANA’s programs.

marro replaced with aute lymphoblastic lukemia

New approach to maintenance chemotherapy may improve children’s quality of life

marro replaced with aute lymphoblastic lukemia

Marrow replaced with acute lymphoblastic leukemia.

According to a study that accrued over 9,000 patients, a new approach to maintenance therapy lessens the burden of treatment and potential toxicity in children experiencing the most common cancer — B-acute lymphoblastic leukemia (B-ALL). The average-risk (AR) B-ALL subset of patients demonstrated an overall five-year survival rate of 98% despite less frequent chemotherapy pulses. Researchers from Children’s National Hospital led the 10-year study published on Jan. 7, 2021, in the Journal of Clinical Oncology.

This phase III clinical trial, which opened at over 200 centers, helped inform an alternative maintenance therapy with less frequent administration of vincristine and dexamethasone. These standard drugs are part of a multiagent treatment approach used to treat acute lymphoblastic leukemia (ALL).

“For decades, the common maintenance therapy approach [within the Children’s Oncology Group] was administering vincristine or steroid pulses every four weeks. The steroids can trigger disruptive behaviors like moodiness, sleep disturbance, food cravings, poor school attendance or physical aggression and vincristine can cause declines in fine motor and sensory-perceptual performance,” said Anne Angiolillo, M.D., lead author of the study and director of the Leukemia and Lymphoma Program at Children’s National. “We can now lessen the burden of this therapy while still maintaining excellent outcomes, which is a huge benefit to our patients and their families.”

The findings suggest that the decreased frequency of both vincristine and dexamethasone pulses every four weeks to every 12 weeks alleviates the therapy burden and reduces toxicity, potentially improving children’s quality of life.

Simultaneously, the researchers tried increasing the starting dose of oral methotrexate, a standard chemotherapy drug, given once weekly in the maintenance phase to see if it would improve the five-year disease-free survival rate, but, according to the data, it did not improve outcomes.

The world’s largest organization devoted exclusively to pediatric cancer research, the Children’s Oncology Group (COG), adopted the approach of less frequent pulses into the frontlines of their new B-ALL trials, given the study’s findings, to help decrease the therapy burden for patients and their families.

“I am very excited that the results of AALL0932 [the clinical trial] will have a major effect on the schedule of maintenance therapy for children with standard and high-risk B acute lymphoblastic leukemia in all future COG therapeutic trials,” said Dr. Angiolillo.

Dr. Angiolillo, and co-author Reuven Schore, M.D., pediatric oncologist at Children’s National were the chair and vice-chair of the clinical trial, respectively. Dr. Schore is also a member of the Leukemia and Lymphoma Program at Children’s National.

ALL can progress quickly, affect the bone marrow and the blood, including B cells and T cells. Among the children with ALL, approximately 55% comprise of the newly diagnosed National Cancer Institute (NCI) standard-risk (SR) B-ALL.

The study enrolled 9,229 patients with B-ALL between August 2010 and March 2018. Only 2,364 patients classified as average-risk received a random assignment to one of the four maintenance arms at the start of maintenance therapy. The researchers administered either vincristine/dexamethasone pulses every 12 weeks or every four weeks and a starting dose of once-weekly oral methotrexate of 20 mg/m2 or 40 mg/m2 during the maintenance phase.

“This trial establishes that with improved risk stratification utilizing blast cytogenetics and rate of response, a relatively low-intensity premaintenance backbone with a three-drug induction, and lower exposure to chemotherapy in maintenance, results in outstanding outcomes,” said Angiolillo et al.

Karun-Sharma-and-kids-MR-HIFU

FDA approves MR-HIFU system to treat osteoid osteoma

Karun-Sharma-and-kids-MR-HIFU

“This FDA approval encourages and further motivates our focused ultrasound program to continue to develop and expand clinical applications of MR-HIFU in the pediatric population,”  said Karun Sharma, M.D., Ph.D.

After garnering successful clinical trial results at Children’s National Hospital, the United States Food and Drug Administration (FDA) recently announced the approval of Profound Medical’s Sonalleve MR-guided High Intensity Focused Ultrasound (MR-HIFU) system for the treatment of osteoid osteoma (OO) in the extremities. OO is a benign, but painful bone tumor that occurs most commonly in children and young adults. This marks the first focused ultrasound regulatory approval that will directly impact pediatric patients and it is the sixth indication to earn approval in the United States.

Nine patients were treated in a pilot trial designed to evaluate the safety and feasibility of MR-HIFU ablation treatment in patients with painful OO. The procedure was performed without any technical difficulties or serious adverse events in all nine patients, and resulted in complete pain relief with no further pain medication usage in eight out of nine patients.

“This FDA approval encourages and further motivates our focused ultrasound program to continue to develop and expand clinical applications of MR-HIFU in the pediatric population,” said Karun Sharma, M.D., Ph.D., director of Interventional Radiology and associate director of clinical translation at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National. “This completely non-invasive and radiation-free aspects of this therapy are especially relevant for growing children.”

Researchers at Children’s National have moved beyond OO are also evaluating MR-HIFU treatment for patients with relapsed and refractory bone and soft tissue tumors. “This is especially important as these patients don’t have any other good treatment options,” said Dr. Sharma. “For these tumors, we are using not only thermal ablation, but also other modes and biomechanisms of focused ultrasound such as mild hyperthermia to facilitate targeted, enhanced drug delivery and histotripsy (i.e., mechanical tissue fractionation) to enhance cancer immunotherapy. We also hope to move into MR-HIFU brain application in pediatrics.”

At Children’s National, a multidisciplinary team of physicians and scientists use MR-HIFU to focus an ultrasound beam into lesions to heat and destroy the tissue in that region, with no incisions at all. In 2015, Children’s National doctors became the first in the U.S. to use MR-HIFU to treat pediatric osteoid osteoma. The trial, led by Dr. Sharma, demonstrated early success in establishing the safety and feasibility of noninvasive MR-HIFU in children as an alternative to the current, more invasive approaches to treat these tumors. Since then, the Children’s National team has built an active clinical trials program and become a leader in translation of focused ultrasound for the treatment of relapsed pediatric solid tumors.

Roger Packer at lectern

Roger Packer, M.D., presents keynote address at First International Pakistan Neuro-Oncology Symposium

Roger Packer at lectern

During his presentation, he addressed attendees on the topic of the “Modern Management of Medulloblastoma,” discussing results of recently completed clinical trials and the implications of new molecular insights into medulloblastoma, the most common childhood malignant brain tumor.

In late November 2020,  Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, presented as the inaugural keynote speaker for the First International Pakistan Neuro-Oncology Symposium in Karachi, Pakistan.

During his virtual presentation, he addressed attendees on the topic of the “Modern Management of Medulloblastoma,” discussing results of recently completed clinical trials and the implications of new molecular insights into medulloblastoma, the most common childhood malignant brain tumor.

The symposium attracted participants from 57 countries across the globe. There were over 1,000 attendees and as a result of the success of this symposium, there is now a monthly pediatric neuro-oncology lecture series. Dr. Packer agreed to lecture again to the group in mid-January 2021 on “Pediatric Neural Tumors Associated with NF1” as part of an international lecture series hosted by the Aga Khan University in Pakistan.

This is one of multiple national and international activities led by the Brain Tumor Institute at Children’s National Hospital. Directed by Dr. Packer with Eugene Hwang, M.D. as his co-director, and who is associate division chief of oncology at Children’s National Hospital, the multidisciplinary institute holds a monthly tumor board for colleagues at Dmitry Rogachev National Research Center and the Burdenko Neurosurgery Institute in Moscow, Russia, and a monthly brain tumor board coordinated by the Pediatric Oncology Program for colleagues across São Paulo, Brazil.

This also leads to a bi-monthly regional tumor board, which is attended by staff of the National Cancer Institute, the University of Virginia, Inova Children’s Hospital, the University of Maryland Children’s Hospital, Children’s Hospital of Richmond at VCU, Children’s Hospital of The King’s Daughters Health System, Yale University, Geisinger Medical Center, Georgetown University and Carilion Clinic.

conceptual image of bladder cancer

Sensitivity to physical versus chemical factors in CAP

conceptual image of bladder cancer

To date, reactive oxygen species and reactive nitrogen species have been regarded as the key factors causing the observable cellular death of cold atmospheric plasma (CAP)-treated cancer cells. The chemical basis of the conventional CAP treatment highlights apoptosis as the main CAP-triggered cell death mechanism.

However, in a recent study published in the Journal of Physics, Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital, and other experts demonstrated a strong anti-melanoma effect based on physically-based CAP treatment. The study, which also tested bladder cancer, compared the anti-cancer effect of chemically-based versus physically-based CAP treatment on four typical cancer cell lines in vitro.

Research & Innovation Campus

Virginia Tech, Children’s National Hospital award $100,000 to fund collaborative cancer research pilot projects

Research & Innovation Campus

This pilot research program represents a growing academic research partnership between Children’s National and Virginia Tech. Last year, the two institutions announced that Virginia Tech will establish a biomedical research facility on the Children’s National Research & Innovation Campus.

Children’s National Hospital and Virginia Tech have awarded two $50,000 one-year pilot grants to multi-institutional teams of scientists for pediatric brain cancer research.

The inter-institutional program, which launched in December, promotes cross-disciplinary collaborations among researchers at both institutions. At Virginia Tech, the program is part of the Virginia Tech Cancer Research Alliance. Financial support for the program was provided by the Offices of the Physician-in-Chief and Chief Academic Officer at Children’s National, and by Virginia Tech’s Office of the Vice President for Health Sciences and Technology.

“We were delighted to see so many innovative and competitive research proposals for our first round of pilot grants in the area of brain cancer. By forging new research collaborations with our partners at Children’s National, we hope to make major strides in addressing one of the most common and devastating groups of cancers in children,” said Michael Friedlander, Virginia Tech’s vice president for health sciences and technology, and the executive director of the Fralin Biomedical Research Institute at VTC. “The pilot funding will bootstrap several programs to be able to acquire ongoing sustainable funding by providing the opportunity to test novel high impact ideas for new strategies for treating these disorders. There are simply too few good options for children in this space now and this partnership can change that for the better.”

The collaborative research initiative began through an agreement between the Fralin Biomedical Research Institute and the Children’s National Research Institute. The collaborative teams formed through a series of interactive discussions among Virginia Tech’s Cancer Research Alliance faculty members from the university’s Blacksburg and Roanoke campuses, and Children’s National’s neuro-oncology researchers.

“I am extremely excited by this collaboration between VT and CNH that is focused on pediatric brain tumors which is such an area of unmet need,” said Catherine Bollard, M.D., M.B.Ch.B.,, director of Children’s National’s Center for Cancer and Immunology Research. “I am confident that the funded proposals will soon advance our understanding of pediatric brain tumors and, more importantly, facilitate more joint efforts between two world-class institutions which is especially timely with the development of the Children’s National Research & Innovation Campus.”

Yanxin Pei, Ph.D., an assistant professor in the Center for Cancer Immunology Research at Children’s National, and Liwu Li, Ph.D., a professor of biological sciences in Virginia Tech’s College of Science, were awarded one of the pilot research grants to study how white blood cells called neutrophils are involved in metastatic MYC-driven medulloblastoma, an aggressive type of brain tumor in children that often resists conventional radiation and chemotherapies.

Yuan Zhu, Ph.D., the Gilbert Family Professor of Neurofibromatosis Research at Children’s National, and Susan Campbell, Ph.D., an assistant professor of animal and poultry sciences in Virginia Tech’s College of Agriculture and Life Sciences, were awarded funds to study glioma-induced seizures in mice with a genetic mutation that inhibits the production of P53, a key protein involved in suppressing cancer cell growth and division.

The successful applicants will receive funding starting this month and are expected to deliver preliminary data to support an extramural research application by 2024.

This pilot research program represents a growing academic research partnership between Children’s National and Virginia Tech. Last year, the two institutions announced that Virginia Tech will establish a biomedical research facility on the Children’s National Research & Innovation Campus. It will be the first research and innovation campus in the nation focused on pediatrics when it opens later this year and will house newly recruited teams of pediatric brain cancer researchers.

Liwu Li, Yanxin Pei, Susan Campbell, and Yuan Zhu

Liwu Li, Ph.D., Yanxin Pei, Ph.D., Susan Campbell, Ph.D., and Yuan Zhu, Ph.D., were awarded funding through the new pilot research program.

Lee Beers

Lee Beers, M.D., F.A.A.P, begins term as AAP president

Lee Beers

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
  • Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
  • Implementation of the AAP’s Equity Agenda and Year 1 Equity Workplan.

Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.

“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”

Read more about Dr. Beer’s career and appointment as president of the AAP.

Roger Packer with patient

A lifetime of achievements: Roger Packer, M.D.

Roger Packer with patient

Over the years, Dr. Packer and his team in Washington, D.C., have made meaningful contributions to children all around the world diagnosed with childhood brain tumors, including medulloblastoma and gliomas.

Earlier in December, Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, received the 2020 Lifetime Achievement Award from the International Symposium on Pediatric Neuro-Oncology at the meeting organized in Karuizawa, Japan. The prestigious recognition is a testament to the years of commitment and dedication Dr. Packer has devoted to the care of children with brain tumors and as such, have placed him as a top leader.

This award is a recognition of how the field has grown since the first International Symposium on Pediatric Neuro-Oncology Dr. Packer organized in Seattle in 1989. “It grew from a small gathering of investigators to now a multidisciplinary group of over 2,000 investigators,” Dr. Packer says.

Over the years, Dr. Packer and his team in Washington, D.C., have made meaningful contributions to children all around the world diagnosed with childhood brain tumors, including medulloblastoma and gliomas. These findings have contributed to an increase of the survival rate from 50% to over 80% for children with medulloblastoma. In addition, his contributions have led to newer molecular targeted therapies and improved the quality of life of children who are long-term survivors.

“The field, especially in the last decade, rapidly transitioned to a more biologically informed field,” Dr. Packer explains. “We are now utilizing new, exciting discoveries in biology and genetics to inform new approaches to treatment. This kind of transition gives us great hope for the future.”

In his early career, Dr. Packer worked with two neuro-oncology patients who died and would impact his decision to further study this field. At that time, there was minimal understanding of the nature of neuro-oncology diseases or how to best treat them. As a neurologist, he was frustrated by the lack of understanding and as a pediatrician, he was frustrated at the lack of ability to do success management.

“I saw this as a gap in my personal knowledge and found that the field was struggling to come up with new answers and new approaches,” he says. “But at the same time other, advances were being made in child cancer care, such as with leukemia. However, there was no wide focus on pediatric brain tumors.”

Combining his knowledge of neurology with his curiosity and relying on other leaders that surrounded him in the same field, Dr. Packer worked on driving this new work forward. Today, he is still heavily involved in the development of treatment protocols that are increasingly transitional for a variety of brain tumors, including low-grade and high-grade gliomas.

“With the help of our great colleagues at Children’s National, we continue to try to develop new means to treat these tumors, including immunological approaches and the incorporation in the use of novel means, such as low-intensity and high-intensity focused ultrasound,” he says. “We also have an excellent multidisciplinary team at Children’s National that has grown over the last decade some of whom are acknowledged national leaders in the fields of brain tumors, clinical research and clinical care. We also have a robust program focusing on the neurocognitive outcome of children and ways to intervene to ameliorate intellectual compromise and improve quality of life.”

DNA moleucle

Epigenetics and pediatric brain tumors

DNA moleucle

Over the last two decades the critical role of epigenetics in cancer biology has evolved significantly. In parallel, our understanding of the biology of many pediatric brain tumors and the central role of alterations in their epigenetic regulation has become an important area of discovery.

In an editorial in a special issue of the Journal of Neuro-OncologyRoger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, looks at understanding the role of epigenetics and how they will further characterize pediatric brain tumors, open new therapeutic avenues for treatment and lead to true breakthroughs and cures for children.

person with brain tumor

Update on pediatric brain tumors

person with brain tumor

Over the last five years, there has been tremendous growth in the field of pediatric neuro-oncology with increasing understanding of the genetic and epigenetic heterogeneity of central nervous system (CNS) tumors. Attempts are underway to translate these insights into tumor-specific treatments. A recent review article in Current Neurology and Neuroscience Reports by Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, provided an update on the current landscape of pediatric brain tumors and the impact of novel molecular insights on classification, diagnostics and therapeutics.

blood cells with sickle cell anemia

Advances in therapy for sickle cell disease and hemophilia

blood cells with sickle cell anemia

Despite having a network of providers and a national database, access to care and treatment burden continue to be issues that affect quality of life in the hemophilia population.

Hemophilia and sickle cell are disorders that are associated with comorbidities and significant treatment burden, discussed Christine Guelcher, PPCNP-BC, lead advanced practice provider for the Center for Cancer and Blood Disorders at Children’s National Hospital, during the virtual 62nd ASH Annual Meeting and Exposition.

During the satellite symposia, Guelcher explained a network of hemophilia treatment centers (HTCs) was developed in the 1970s. The model of multi-disciplinary care in the HTC network has demonstrated improved outcomes. Despite having a network of providers and a national database, access to care and treatment burden continue to be issues that affect quality of life in the hemophilia population.

“While similar programs were developed in sickle cell with similar improvements in care, the funding was not sustained,” Guelcher said. However, efforts are underway to develop multi-disciplinary care and data infrastructure in the sickle cell community.

“The lack of specialized providers, particularly adult hematologists, continues to be an issue for both non-malignant hematologic disorders,” she added.

Advances in care

While hemophilia is rare, it is an expensive disease. Controlling bleeding with medications is expensive and associated with significant treatment burden. Failure to prevent bleeding due to lack of access or adherence can result in debilitating bleeding that impacts on productivity and quality of life. Additionally, clinical trials with gene therapy are ongoing, though questions remain about sustained levels and durability.

“Recent development of drugs that can reduce the frequency of intravenous infusions (extended half-life factor replacement products or subcutaneous novel non-factor prophylaxis) have improved the treatment burden,” Guelcher said. “But access to care continues to be an issue for up to 30% of the patients with bleeding disorders in the U.S.” Sickle cell disease affects mostly Black/African American and Hispanic patients, many of whom already experience health care disparities. While newborn screening, antibiotic prophylaxis and immunizations have decreased life-threatening infections, vaso-occlusive (pain) crisis continues to be a debilitating complication. Furthermore, stroke, pulmonary, cardiac and renal disease are significant comorbidities.

While advances in therapies for sickle cell have provided new treatment options to decrease the frequency of vaso-occlusive crisis, the pathophysiology that results in all of the sequalae is not fully understood. While Bone marrow transplant is potential treatment of the underlying sickle cell disease process, only 20% of patients have a matched sibling donor. Currently, clinical trials are investigating the safety and efficacy of gene therapy. Despite all of these advances, the life expectancy of somebody with sickle cell is 30 years shorter than the general U.S. population.

Access to care

The multi-disciplinary panel presentation at ASH gave participants an opportunity to hear about the challenges facing these patients and families. The overview of new and emerging treatment options gave providers an understanding of treatment options.

“Hopefully, presentations like this will inspire providers to consider a career in non-malignant hematology (particularly adult providers),” Guelcher added.

As one of the nation’s hemophilia and thrombosis treatment centers, Children’s National Hospital provides comprehensive, multi-disciplinary care. Patients can participate in two national registries in order to collect aggregate data that are used to identify trends that impact bleeding disorder patients. Our sickle cell program also offers multi-disciplinary clinics for infants, integrative care for chronic pain and transition, addressing some of the unmet needs that continue to be an issue nationally.

“We also participate in industry sponsored clinical trials to ensure that new therapies, including gene therapy, are safe and effective,” Guelcher explained. “This gives our patients access to state-of-the-art care. Numerous clinical trials to ensure that recently licensed products and gene therapy are safe for use in a pediatric patient with hemophilia and sickle cell are ongoing.”

Roger Packer

Roger Packer, M.D., receives Lifetime Achievement Award

Roger Packer

“I am very honored and humbled to receive this recognition from the International Symposium on Pediatric Neuro-Oncology,” says Roger Packer, M.D. “I am proud of the contributions my team and I have made in this field and we look forward to continue to lead research focused on the advancement of the crucial areas neuro-oncology.”

Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, will receive the 2020 Lifetime Achievement Award from the International Symposium on Pediatric Neuro-Oncology. Dr. Packer was selected as a recipient for the prestigious award for his substantial contributions to pediatric oncology and scientific achievements.

“I am very honored and humbled to receive this recognition from the International Symposium on Pediatric Neuro-Oncology,” says Dr. Packer. “I am proud of the contributions my team and I have made in this field and we look forward to continue to lead research focused on the advancement of the crucial areas neuro-oncology.”

Dr. Packer is also a Gilbert Distinguished Professor of Neurofibromatosis and is Director of both the Gilbert Neurofibromatosis Institute and the Brain Tumor Institute of Children’s National Hospital. Most of the current studies Dr. Packer coordinates are studies evaluating innovative agents aimed at the molecular underpinnings of neurologic disease. He has published over 400 original articles and 350 reviews and chapters.

The award will be presented at ISPNO 2020, the 19th International Symposium on Pediatric Neuro-Oncology, December 13-16, 2020, in Karuizawa, Japan.

Children’s National Hospital is incredibly proud of the work Dr. Packer has done in the neuro-oncology community.

graphic abstract for brain tumor paper

First large-scale proteogenomic analysis offers insights into pediatric brain tumor biology

graphic abstract for brain tumor paper

In the first large-scale, multicenter study of its kind, researchers conducted comprehensive analysis yielding a more complete understanding of pediatric brain tumors (PBT), which are the leading cause of cancer-related deaths in children. Researchers from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Children’s Brian Tumor Network (CBTN) generated and analyzed proteomic data, which identifies common biological characteristics among different tumor types. The consortia consist of collaborators from the Icahn School of Medicine at Mount Sinai, National Cancer Institute, Fred Hutchinson Cancer Research Center, Children’s National Hospital and Children’s Hospital of Philadelphia. The study, published in Cell on November 25, 2020, provides a clearer understanding of the molecular basis of pediatric brain tumors and proposes new therapeutic avenues.

The molecular characterization of brain tumors has largely hinged upon the presence of unique alterations in the tumor genome ignoring the many layers of regulation that exist between DNA and the functional biology of the tumor cell that is actuated by proteins. The integration of proteomic data identifies common biological themes that span histologic boundaries, suggesting that treatments used for one histologic type may be applied effectively to other tumors sharing similar proteomic features.

Brian Rood, M.D., medical director of the Brain Tumor Institute and associate professor of pediatrics in the Center for Cancer and Blood Disorders at Children’s National Hospital, participated in this study and explains the importance of what the team discovered.

Q: Why was it important that researchers came together to do this work?

A: Comprehensive characterization of the fundamental biology of pediatric brain tumors, including the proteogenomic analysis done in this study, is essential to better understand and treat pediatric brain tumors.

Our study is based on the recognition that proteomics and phosphoproteomics needs to be integrated with other omics data to gain an improved systems biology view of the molecular features of brain tumors. In addition, characterizing biological themes that cross histologic boundaries and cells of origin can suggest extending treatments shown to be effective in one type of tumor to other histologically disparate tumors sharing the same proteomic features.

Proteomic data further reveal the functional impacts of somatic mutations and copy number variations (CNVs) not evident in transcriptomic data alone. Further, kinase-substrate network analyses identify activated biological mechanisms of tumor biology.

This work was only possible because of a unique collaboration between the CPTAC program of the NCI and the CBTN, of which Children’s National is a member.

Q: How will this work advance understanding and treatment of pediatric brain tumors?

A: Pediatric brain tumors have not benefitted from molecularly targeted drugs as much as other tumor types largely because they harbor relatively few gene mutations. Therefore, identifying key pathways to target in these patients’ tumors has been a challenge. The integration of proteomic and phosphoproteomic data with genomic data allows for the construction of a more comprehensive model of brain tumor biology and nominates specific key pathways to be targeted.

Q: What did you find that excites you?

A: Proteomic data revealed a number of findings that were not present in the genomic data. We found evidence to support a molecularly targeted approach to treating craniopharyngioma, a tumor that has previously been unresponsive to chemotherapy. We also found a prognostic marker for high grade gliomas that do not have a mutation in the H3 histone. We were able to identify specific kinases that may dictate the aggressive nature of certain ependymoma tumors. Importantly, we demonstrated the potential of proteomic studies to uncover unique tumor biology, paving the way for more extensive investigations using this approach.

You can find the full study published in Cell. Learn more about the Brain Tumor Institute at Children’s National.


Dr. Rood recently joined a live panel discussion with researchers from the Children’s Brain Tumor Network and the Clinical Proteomic Tumor Analysis Consortium to explore the impact of their landmark study.

tumor cells

Promising new pediatric oncologic applications for focused ultrasound

tumor cells

Earlier this month, AeRang Kim, M.D., Ph.D., oncologist at Children’s National Hospital, spoke at the Focused Ultrasound Foundation’s 7th International Symposium on Focused Ultrasound about the latest developments in focused ultrasound applications for pediatric oncology.

Dr. Kim and a team of researchers at Children’s National belong to the IGNITE (image guided non-invasive therapeutic energy) team, a multidisciplinary group working to develop and transform focused ultrasound applications that will minimize treatment side effects and increase efficacy in pediatric cancer care.

In 2015, the IGNITE team conducted its first trial with a study of MR-guided high-intensity focused ultrasound (MR-HIFU) for treating painful osteoid osteomas (a benign bone tumor) in children. This was followed by a trial of MR-HIFU ablation for pediatric solid tumors.

“MR-HIFU has a potential role in local treatment of tumors, both benign and malignant,” Dr. Kim said. “What I’m most excited about is that MR-HIFU has the flexibility to be combined with other treatments such as heat sensitive targeted therapy and immune therapy. I believe this combination approach will have the highest impact in terms of safety and efficacy in pediatric cancer care.”

Aerang Kim

“MR-HIFU has a potential role in local treatment of tumors, both benign and malignant,” says AeRang Kim, M.D., Ph.D. “What I’m most excited about is that MR-HIFU has the flexibility to be combined with other treatments such as heat sensitive targeted therapy and immune therapy.”

Focused ultrasound is an emergent, non-invasive therapeutic technology that uses ultrasonic energy to target tissue deep in the body without incisions or radiation, thus resulting in minimal discomfort and few complications. This also allows for rapid patient recovery. The applications are wide-ranging: from thermal ablation of tumors and other lesions to blood-brain barrier opening, to increasing tumor vasculature for improved drug delivery, to augmenting immune response, among many others.

The team is now working on combinations of focused ultrasound with other therapies, such as chemotherapy. On the third clinical trial open for accrual at Children’s National, they combine MR-HIFU with lysothermosensitive liposomal doxorubicin, a heat-activated form of the cancer drug doxorubicin, to treat pediatric solid tumors. Although results are still preliminary, the hope is that the technology will mitigate some of the acute and late effects of current multimodal therapy in children. “We want to provide more efficacy and precision with these therapies,” said Dr. Kim.

In reflecting on the potential of this new approach, Dr. Kim believes the findings can help change the way experts think about cancer treatment.  The team is studying pre-clinical models of pediatric cancer to evaluate the different modalities of MR-HIFU with immune checkpoint inhibitors. Understanding that there are limitations of MR-HIFU ablation alone, Dr. Kim believes the future for most pediatric cancer applications will be combining approaches using the various bioeffects of focused ultrasound.

“We hope that if promising effects in multiple models utilizing this combination, we can translate these findings into the clinical setting,” she said, noting that the clinical trials led by her team are among the first in the U.S. of HIFU for children. “Children’s National is one of the first pediatrics centers to lead a HIFU program and the Focus Ultrasound Foundation’s first Center of Excellence focused exclusively in pediatrics.  We hope to continue to expand our findings and improve pediatric cancer care that’s more precise, less toxic, less invasive and pain free.”

Research & Innovation Campus

Boeing gives $5 million to support Research & Innovation Campus

Research & Innovation Campus

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus.

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus. The campus, now under construction, is being developed on nearly 12 acres of the former Walter Reed Army Medical Center. Children’s National will name the main auditorium in recognition of Boeing’s generosity.

“We are deeply grateful to Boeing for their support and commitment to improving the health and well-being of children in our community and around the globe,” said Kurt Newman, M.D., president and CEO of Children’s National “The Boeing Auditorium will help the Children’s National Research & Innovation campus become the destination for discussion about how to best address the next big healthcare challenges facing children and families.”

The one-of-a-kind pediatric hub will bring together public and private partners for unprecedented collaborations. It will accelerate the translation of breakthroughs into new treatments and technologies to benefit kids everywhere.

“Children’s National Hospital’s enduring mission of positively impacting the lives of our youngest community members is especially important today,” said Boeing President and CEO David Calhoun. “We’re honored to join other national and community partners to advance this work through the establishment of their Research & Innovation Campus.”

Children’s National Research & Innovation Campus partners currently include Johnson & Johnson Innovation – JLABS, Virginia Tech, the National Institutes of Health (NIH), Food & Drug Administration (FDA), U.S. Biomedical Advanced Research and Development Authority (BARDA), Cerner, Amazon Web Services, Microsoft, National Organization of Rare Diseases (NORD) and local government.

The 3,200 square-foot Boeing Auditorium will be the focal point of the state-of-the-art conference center on campus. Nationally renowned experts will convene with scientists, medical leaders and diplomats from around the world to foster collaborations that spur progress and disseminate findings.

Boeing’s $5 million commitment deepens its longstanding partnership with Children’s National. The company has donated nearly $2 million to support pediatric care and research at Children’s National through Chance for Life and the hospital’s annual Children’s Ball. During the coronavirus pandemic, Boeing fabricated and donated 2,000 face shields to help keep patients and frontline care providers at Children’s National safe.