Cancer

Jia-Ray Yu

Virginia Tech announces cancer biologist to launch lab at Children’s National Research & Innovation Campus

Jia-Ray Yu

Jia-Ray Yu, Ph.D., will be an assistant professor at Virginia Tech’s Fralin Biomedical Research Institute at Virginia Tech Carilion and in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine, as well as an adjunct assistant professor at Children’s National Hospital starting Sept. 1.

Every year, 790 Americans are diagnosed with a rare and deadly form of brain cancer called a diffuse midline glioma, according to the National Cancer Institute. Tragically, only 2% of children with this disease will survive five years.

Jia-Ray Yu, Ph.D., a new assistant professor joining the Fralin Biomedical Research Institute at Virginia Tech Carilion and the Department of Biomedical Sciences and Pathobiology on Sept. 1, studies these fast-growing, treatment-resistant brain tumors, which commonly affect children, with hopes of identifying new therapeutic approaches. Yu will be the first of several cancer researchers to work in Virginia Tech’s brand-new research facility on the Children’s National Research & Innovation Campus in Washington, D.C.

“This disease is fatal and there is no cure. Any hint at a potential therapeutic pathway could be helpful,” said Yu, who will also hold an adjunct faculty position in the Children’s National Hospital Center for Cancer and Immunology Research.

Michael Friedlander, Virginia Tech’s vice president for health sciences and technology, and executive director of the Fralin Biomedical Research Institute, led Yu’s recruitment.

“Jia-Ray Yu is one of the rising leaders in understanding the molecular substrates of aggressive forms of pediatric brain cancer that can contribute to the identification of innovative therapeutic approaches. Moreover, his fundamental research into chromatin remodeling is at the very forefront of this area of emerging area importance in molecular biology,” Friedlander said. “We are very fortunate to have been able to attract Dr. Yu to Virginia Tech as we grow our greater cancer research community and our partnership with one of the nation’s pre-eminent children’s health care delivery and research systems, Children’s National Hospital.”

Yu studies how genes change when an ordinary brain cell develops malignant traits.

In particular, he examines changes in proteins called histones that spool strands of DNA molecules into a substance called chromatin, which forms chromosomes. In addition to packing genetic material into cells, these structures also play a key role in telling genes when to turn on or off.

Faulty histone proteins alter the chromatin’s structure, which in turn garbles the genetic instructions that regulate a cell’s behavior, growth rate, and identity. Furthermore, when this defective cell divides, its two daughter cells inherit the original cell’s chromatin, the malignant traits are passed on, and the cancer grows.

“These epigenetic features of chromatin are distinct from the DNA itself, yet they are inherited during cellular division,” said Yu.

Yu said 80% of tumors from diffuse midline gliomas begin with one cell that has a histone gene defect. He found when this tiny piece of a specific histone, called H3K27, stops working properly, it creates a series of domino-like reactions that cause normal cells to become cancerous.

Yu recently examined this molecular cascade as a postdoctoral fellow in the lab of Danny Reinberg, Terry and Mel Karmazin Professor in the NYU Grossman School of Medicine Department of Biochemistry and Molecular Pharmacology, and senior Howard Hughes Medical Institute Investigator.

The research team identified two genes, NSD1 and NSD2, appear to be the molecular fingers that tap the histone domino. When these genes are disabled, diffuse midline gliomas stop growing in a cultured lab dish, and in animal models. They also identified signaling pathways that could be targets for new drug therapies. Their findings are available in pre-print and will be published this summer in Science Advances.

Yu’s laboratory at the new Children’s National Research & Innovation Campus in Washington, D.C., will build on this fundamental question: How can chromatin-associated molecules be targeted to stop aggressive cancers?

Yu says that as he studies the molecular genesis of diffuse midline glioma, he may also identify therapeutic approaches for other diseases, such as leukemia and Sotos syndrome, that involve mutations in these chromatin-associated molecules.

His research team will combine biochemistry, single-molecule imaging, next-generation sequencing, biophysics, and preclinical research to develop and test new pharmaceutical alternatives to chemotherapy and radiation.

Yu was awarded a three-year American Cancer Society Postdoctoral Fellowship while working in Reinberg’s laboratory.

He completed a bachelor’s degree in biological science and technology at National Chiao Tung University in Taiwan, and his doctoral degree in genetics at Stony Brook University and Cold Spring Harbor Laboratory, where he studied signaling pathways in lung adenocarcinoma metastasis.

Recruitment for research positions in the Yu lab begins this summer.

Deepika Darbari

Deepika Darbari, M.D., receives the 2021 ASH Award for leadership in promoting diversity

Deepika Darbari

Deepika Darbari, M.D., hematologist at Children’s National Hospital, is being honored by the American Society of Hematology (ASH) for her significant contributions to the mentorship and training of underrepresented minority researchers and for advancing the care for underrepresented patient populations, primarily individuals living with sickle cell disease (SCD). Dr. Darbari started studying and treating SCD at Howard University, where she also saw firsthand the many disparity issues surrounding the condition, such as inadequate funding, limited treatment options and biases and stigma. She also learned about barriers to career development that minority students faced. She worked to address those issues through her mentorship.

Dr. Darbari has mentored many medical students, residents and fellows whose research projects focused on improving care for individuals living with SCD. She has also fostered the careers of junior investigators of underrepresented minorities as well as served as a member of the ASH Minority Medical Student Award Program, the ASH Committee on Promoting Diversity and the ASH Women in Hematology working group, all in her continued efforts to increase diversity, equity and inclusion at ASH and in the health care community at large.

cancer cell

Muller Fabbri, M.D., Ph.D.: The microRNA journey and the future of cancer therapy

cancer cell

Children’s National Hospital welcomes Muller Fabbri, M.D. Ph.D., as associate director for the Center for Cancer and Immunology Research at the Children’s National Research Institute. In this role, he will build and lead the Cancer Biology Program while developing and conducting basic and translational research. Dr. Fabbri will also develop multidisciplinary research projects with various clinical divisions, including oncology, blood and marrow transplantation, pathology and hematology.

Dr. Fabbri shares his journey working with microRNAs, how his work is advancing the field and his vision for the Center for Cancer and Immunology Research at Children’s National.

Q: You have been working with microRNAs for quite some time. How are you exploring the role of microRNAs in cancer?

A: It was well established within the scientific community that a gene, which is a piece of DNA, becomes a piece of RNA and then becomes a protein. This thought process was pretty much a one-way flow of information that we had, going from DNA to protein as part of a cell function. But, almost 30 years ago, it was discovered that this is not entirely true because what happens is that some of these genes that are transcribed into RNA do not become a protein. Instead, they stay as RNA. Some of these RNAs are tiny and have short sequences, which is why they are called microRNAs.

I work primarily on microRNAs and non-coding RNAs and my research studies focus on the role that microRNAs play in cancer. I can take a cancer cell and a healthy cell and observe how these microRNAs are expressed in the two different cell populations. In this way, the microRNAs expressed in cancer cells are profoundly different from the microRNAs expressed in healthy cells.

We conducted a series of studies to observe what happens to a cancer cell if we restore normal levels of certain microRNAs like the ones you would see in a normal cell. We discovered that by restoring some of these microRNAs levels it led to the death of the cancer cells, suggesting that this approach may be used as a cancer treatment. This is one of the research areas that I will further develop at Children’s National as I seek to understand the mechanisms that control microRNA expression and subsequently affect cancer cell proliferation. With this information, we can target these mechanisms and create drugs that interfere with this function and, hopefully, stop cancer cell growth.

Q: Can you tell us about that eureka moment with your best friend during a lunch break?

A: This was a bit of a crazy idea. I will never forget. I shared a theory during a lunch break with a friend. I dared to ask, what if microRNAs worked like hormones? MicroRNAs can be detected in the blood of patients with cancer, and they can be transferred from one cell to another inside of little vesicles called exosomes. If you think about it, I further asked, what other molecules in our body behave like that — i.e. are secreted, circulate in the blood and then transferred to a target cell? My friend replied, “well, those would be hormones.” To which, I added, yes, exactly! Then, why do we not think of RNAs as hormones? And I quote him now, “you are crazy, but if it works it is huge.”

I felt that I had some validation from my best friend, so I decided to invest in this crazy idea, carving extra time on the side while working on my “safe” projects. It was one of those rare cases in science, where in a little over a year, we showed for the first time that microRNAs do not only work the traditional way, but they can also work as hormones. They do have a receptor protein to attach to, and by binding to this protein, they trigger a response in a cell that can be pro-tumoral or anti-tumoral.

Even today, if you open a textbook of endocrinology, under the chapter of hormones, it mentions that there are only two categories, proteins and lipids. Well, it turns out there is a third category, which is nucleic acids because of RNAs.

Q: You mentioned other research areas of interest as it relates to cancer cell biology. What are they?

A: The other line of research that I am developing stems from the original observation that I made in 2012. Cancer cells release tiny vesicles that I like to compare to envelopes containing a written message — the RNA and microRNA. These vesicles released in the surrounding environment contain a message captured by immune cells, known as macrophages. Macrophages act as scavengers in our bodies. In cancer, macrophages are supposed to digest and destroy the cancer cell. However, it turns out that they also have the proper receptor to receive and read the message enclosed in the vesicles. Then, something shocking happens. The macrophage stops fighting the cancer cell and starts producing proteins called cytokines that promote cancer growth. This finding means that we are 180 degrees apart from what we thought at the beginning. A lot of macrophages in the cancer are good news for the patient because they are supposed to kill cancer cells, but because of this mechanism, a lot of macrophages can be bad news since they can also help the cancer cell grow.

My contribution to this discovery was to investigate how the macrophage response is mediated. I discovered that macrophages operate, at least in part, by expressing receptors that bind to microRNAs released by the cancer cell, thereby favoring cancer growth. In the pediatric cancer field we discovered that because of this microRNA–receptor interaction, the pediatric tumor neuroblastoma becomes resistant to chemotherapy. Therefore, one of the strategies we are working on now is to interfere or impair these negative communications between the cancer cell and immune cell. We want to disrupt these communications so the macrophage cannot read the message from the cancer cell anymore and instead keeps doing its job to fight the cancer. We hope that we can leverage this approach to develop novel cancer treatments or create strategies that improves immune cell function in the presence of the patient’s current therapy to enhance an anti-cancer treatment response.

Q: What is your vision for the Center of Cancer and Immunology Research?

A: I am very excited about what I saw at Children’s NationalI was delighted to talk to many faculty members, and I recognized the immense talent within the Center. I would like to help elevate and enhance the cancer biology program focused on solid tumors, and augment the work being done in this space by the cell therapy program. The clinicians are clearly eager to collaborate with the basic scientists including the sharing of samples and ideas, which is not typical of many scientific environments. My other goal is to ensure that the Cancer Biology Program plays a central role in acquiring an NCI-Designated Cancer Center recognition often given to institutions that stand out in scientific leadership and clinical research. Finally, I want to create the first national center that develops extracellular vesicles as an innovative treatment strategy for cancer. Importantly, I think that we have all the resources and connections at Children’s National that are necessary to realize this vision!

 

T cell

Children’s National Hospital scientists shortlisted for Cancer Grand Challenges funding

T cell

If successful, the team would seek to tackle the challenge of solid tumors in children. The vision is to bring engineered T-cell therapies to the routine treatment of these children within a decade.

A diverse, global team of scientists, led by University College of London and Children’s National Hospital/George Washington University, has been selected for the final stages of Cancer Grand Challenges – and is in with a chance of securing a share of £80 million (c.$111 million) of funding to take on one of cancer’s toughest problems.

Nearly 170 teams submitted ideas for this round of awards, and the NGTC team, which stands for ‘Next Generation T-cell therapies for childhood cancers, led by Martin Pule, Ph.D., University College of London, and Catherine Bollard, M.B.Ch.B., M.D., Children’s National Hospital and George Washington University, is one of 11 shortlisted groups.

The team draws together a unique set of expertise, uniting researchers from the U.K., U.S. and France. Other team members from Children’s National include Conrad Russell Cruz, M.D., Ph.D., principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies, and Nitin Agrawal, Ph.D., associate professor in the Center for Cancer and Immunology Research (CCIR). Up to four winning teams will be announced in early 2022.

If successful, the NGTC team would seek to tackle the challenge of solid tumors in children. The team says that the scientific and medical communities are beginning to understand that solid tumors in children are very different from those in adults – if they could understand more about these differences and find new ways to target them, they could create new ways to better treat children’s cancers.

The NGTC team’s vision is to bring engineered T-cell therapies to the routine treatment of these children within a decade.

Through a series of ambitious studies, the team hopes to identify suitable, pediatric tumor-specific targets for engineered T-cells, including previously unexplored options like glycolipids or the immunopeptidome. They also hope to explore whether treatment effectiveness can be boosted by modulating the tumor microenvironment – which can inhibit T-cell therapies but is yet to be suitably studied in children’s cancers. The team has a strong translational focus and the most promising new treatment avenues would be explored in preclinical and early clinical studies.

“We’re tremendously excited to have this opportunity to work together and strive closer to our vision – to improve the lives of the patients we serve,” says joint team lead Dr. Bollard, who is also the director of the Center for Cancer and Immunology Research at Children’s National.

“This round of Cancer Grand Challenges has demonstrated the fresh thinking that can be sparked when global teams unite across disciplines to bring new perspectives to tough challenges,” says Dr. David Scott, Ph.D., director of Cancer Grand Challenges. “We were thrilled to receive such a strong response from the global research community.”

Find out more at cancergrandchallenges.org.

inside a GMP lab

Cell therapy manufacturing process ramps up to meet increased demand for T-cell products

inside a GMP lab

The new laboratory space includes floor-to-ceiling windows and brand new, state-of-the-art GMP lab suites.

Since Children’s National Hospital began its pediatric cellular therapy program in 2013, it has received more than $5 million in annual funding, treated over 200 patients, manufactured more than 400 cell-based products and supported over 25 clinical trials.

One of the in-house programs supporting this work is the Good Manufacturing Practices (GMP) facility. Patrick Hanley, Ph.D., chief and director of the cellular therapy program at Children’s National and leader of the GMP laboratory, explained that the first patient received a dose of less than 10 million cells in May 2014. Fast forward to now, the lab uses liters of media, automated bioreactors and multiple staff, making upwards of 12 billion cells per run — a growing production scale that enables many different options. Using cells as an off-the-shelf technology is one of those.

The cell therapy program exports these off-the-shelf products beyond Children’s National to make them available for kids across the country. Catherine Bollard, M.D., MBChB., director of the Center for Cancer and Immunology Research at Children’s National, and Michael Keller, M.D., director of the Translational Research Laboratory in the Program for Cell Enhancement and Technologies for Immunotherapy (CETI) at Children’s National, each led clinical trials with hospitals across the United States, including the first-ever cellular therapy clinical trial run through the Children’s Oncology Group.

To meet the high demand for cell therapy trials at Children’s National, the GMP lab moved to a larger space, doubling the team’s capacity to produce alternative treatment options for patients and facilitate the lab’s ability to support clinical divisions throughout the hospital.

The GMP lab is exploring how to make cell products more consistent — regardless of patient-to-patient variability. They are also hoping to delineate the characteristics that ensure quality cell products, educate other facilities, enhance the overall knowledge of how to safely manufacture these products and make these technologies more available and affordable to the patients who need them.

Among Hanley’s many goals for the GMP lab, one is to improve the transition from when an investigator discovers a product in the translational research lab to when it is manufactured for patients.

“To improve this transition, we have started a process development team that will learn the process alongside the research team, replicate it, and then train the staff who manufacture the product for patients,” said Hanley. “In addition to providing a better training opportunity for the manufacturing staff, it allows us to work with the investigators earlier on to identify changes that will need to be made to translate the products to patients, ultimately resulting in safer, more potent immunotherapy products.”

While cell therapy has seen increased interest in the last 10 years, there are still some challenges in the field, given that it is not as mature as other scientific areas. The lack of trained staff, scalability of cell and gene therapy, the variability between patients and products, delayed FDA approvals and rejection of licensing applications for cell therapy products — are barriers that scientists and companies often face.

“Each of us has a unique immune system, and that means that if we try and make a product from it, it will not behave like any other, so the number of cells, the potency the alloreactivity — it is all different,” said Hanley. “T-cells are a living drug that expand in the body at different rates, are composed of different types of T-cells, and release different cytokines and in different amounts.”

This all ties back to the process development and basic research. The better researchers can characterize the products under development, the more they will know about how the products work and the easier it will be to tie these products to patient outcomes.

Meet some of the Children’s National multidisciplinary experts who join forces to lead the cell therapy space.

Jay Tanna, M.S., quality assurance manager, has extensive experience with drug development at Children’s National as well as Sloan Kettering, another premier cell therapy institution. He has a Masters in Pharmaceutical Manufacturing and a Regulatory Affairs Certification (RAC) in U.S. FDA drugs and biologics regulations from the Regulatory Affairs Professional Society (RAPS).

Kathryn Bushnell, M.T. (ASCP), the cell therapy lab manager, oversees Stem Cell Processing. She has 20 years of experience with hematopoietic progenitor cells and cellular therapy, starting her career as a medical technologist at MD Anderson Cancer Center.

Nan Zhang, Ph.D., assistant director of manufacturing at Children’s National, has worked at Wake Forest and the National Institutes of Health developing various cellular therapies. Zhang chaired the cell processing session at the annual meeting of the American Society of Hematology in 2020.

Abeer Shibli, M.T., is a specialist in the cellular therapy laboratory with extensive experience in the processing of cellular therapy products. She has over 10 years of experience as a medical technologist, is specialized in blood banking and transfusion medicine and is one of the senior technologists in the lab.

Chase McCann, M.S.P.H., Ph.D., is the cell therapy lab lead for manufacturing at Children’s National Hospital. He recently completed his Ph.D. training in Immunology and Microbial Pathogenesis at Weill Cornell Medicine in New York. Much of his graduate research focused on developing and enhancing cellular therapies for HIV while identifying common mechanisms of escape, shared by both HIV and various cancers, which limit the efficacy of current cell therapies. Previously, McCann worked as the laboratory coordinator for the HIV Prevention Trials Network, and now oversees the manufacturing of many cell therapies supporting the many clinical trials currently underway at Children’s National.

Anushree Datar, M.S., the cell therapy lab lead for immune testing and characterization, oversees the release testing of products manufactured in the GMP for safety and function before they can be infused in patients. She also leads a part of the research team investigating the improvement in immune function after cell infusion.

Dr. Bollard is also the director of the Program for Cell Enhancement and Technologies for Immunotherapy and president of the Foundation for the Accreditation for Cellular Therapy (FACT). Additionally, in 2019, she became a member of the Frederick National Laboratory Advisory Committee (FNLAC) for the NIH and an ad hoc member of the Pediatric Oncologic Drugs Advisory Committee (ODAC) for the FDA. She has been an associate editor for the journal Blood since 2014 and in 2020 was appointed editor-in-chief of Blood Advances (starting Fall 2021). Dr. Bollard has 21 years of cell therapy experience as a physician, sponsor and principal investigator.

Dr. Hanley serves as the commissioning editor of the peer-reviewed journal Cytotherapy, as the vice-president-elect (North America) of the International Society of Cell and Gene Therapy (ISCT), and board of directors member at FACT, which provides him visibility into various cell and gene therapies, manufacturing approaches, and other intangibles that make Children’s National facility one of the leaders in the field.

To find the full research program list and their experts, click here.

GMP group photo

Lab members celebrate the expansion of the GMP Laboratory.

US News badges

For fifth year in a row, Children’s National Hospital nationally ranked a top 10 children’s hospital

US News badges

Children’s National Hospital in Washington, D.C., was ranked in the top 10 nationally in the U.S. News & World Report 2021-22 Best Children’s Hospitals annual rankings. This marks the fifth straight year Children’s National has made the Honor Roll 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 fifth year in a row.

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

“It is always spectacular to be named one of the nation’s best children’s hospitals, but this year more than ever,” says Kurt Newman, M.D., president and CEO of Children’s National. “Every member of our organization helped us achieve this level of excellence, and they did it while sacrificing so much in order to help our country respond to and recover from the COVID-19 pandemic.”

“When choosing a hospital for a sick child, many parents want specialized expertise, convenience and caring medical professionals,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings have always highlighted hospitals that excel in specialized care. As the pandemic continues to affect travel, finding high-quality care close to home has never been more important.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

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.

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

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

Muller Fabbri

Children’s National Hospital welcomes Muller Fabbri, M.D., Ph.D.

Muller Fabbri

Dr. Fabbri joins Children’s National from the University of Hawaii Cancer Center, where he was a tenured associate professor and leader of the Cancer Biology Program. He received his medical degree at the University of Pisa in Italy and his Ph.D. degree at the Second University of Naples in Italy.

Children’s National Hospital is pleased to announce it has selected Muller Fabbri, M.D. Ph.D., as associate director for the Center for Cancer and Immunology Research at the Children’s National Research Institute. In this role, he will build and lead the Cancer Biology Program while developing and conducting basic and translational research. Dr. Fabbri will also develop multidisciplinary research projects with various clinical divisions, including oncology, blood and marrow transplantation, pathology and hematology.

A distinguished lecturer, instructor, researcher, public speaker and mentor, Dr. Fabbri’s research interest focuses on decoding cancer cellular biology riddles that lead to personalized medicine. He has pioneered a theory that explains non-coding RNAs’ functioning in intercellular communication that promotes cancer cell growth, dissemination and drug resistance. To better understand the immune response against cancer cells, he has investigated the role of exosomes and other extracellular vesicles. Inflammation, tumor microenvironment and immunity, as it relates to cancer, are other research areas of interest.

“I feel fortunate to be working with Dr. Catherine Bollard and her team at an extraordinary research center,” said Dr. Fabbri. “I am eager to join Children’s National, and I look forward to learning from this leadership team, which also includes Dr. Vittorio Gallo, Dr. Mark Batshaw and Dr. Jeffery Dome.”

Dr. Fabbri was drawn to Children’s National because of its proximity to partners like the National Institute of Health (NIH), the Food Drug Administration (FDA), various universities and the private sector, fostering a rich scientific environment. One of Dr. Fabbri’s many goals, is to make sure that the Cancer Biology Program plays a central role in the acquisition of an NCI-Designated Cancer Center recognition often given to institutions that stand out in scientific leadership and clinical research.

Dr. Fabbri joins Children’s National from the University of Hawaii Cancer Center, where he was a tenured associate professor and leader of the Cancer Biology Program. He received his medical degree at the University of Pisa in Italy and his Ph.D. degree at the Second University of Naples in Italy.

Dr. Catherine Bollard is accompanied by her mentees

Catherine Bollard, M.D., awarded two notable recognitions

Dr. Catherine Bollard is accompanied by her mentees

Dr. Catherine Bollard and some of her mentees.

For her work on developing cell-based therapies and dedication to her trainees, Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research at Children’s National hospital, receives two outstanding awards in her field.

Celebrating the minds behind the architecture of modern medicine and influencing the drug industry, The Medicine Maker, through an international panel of judges, added Dr. Bollard to the 2021 Power List in the category of advanced medicine.

Dr. Bollard mentioned that it is encouraging to see mRNA vaccine technology successfully fighting the COVID-19 pandemic because it paves the way for cancer vaccine advancements. Still, there are challenges affecting drug development. The centralized manufacturing hinders the large-scale production of patient-specific products as more cell therapies are getting approval, she added.

“Looking to the future, cell-based therapies will not be sustainable with a purely patient-specific centralized manufacturing model and, therefore, the field must move into the development of off-the-shelf cell therapies,” said Dr. Bollard. “The success of off-the-shelf virus-specific T-cells is especially exciting because it has the potential to be the platform for other antigen-specific and CAR-T cell therapies.”

A global society of clinicians, researchers, regulators, technologists and industry partners, The International Society for Cell & Gene Therapy (ISCT), will bestow Dr. Bollard the 2021 ISCT Darwin J. Prockop Mentoring Award on May 26. Her ongoing commitment to mentorship has advanced the careers of many aspiring professionals that have worked alongside her. The ISCT Award Committee selected someone that can inspire the current and future growing workforce. Dr. Bollard is highly recognized across the industry for her leadership, passion and dedication to her mentees, and her extraordinary efforts to advance their skills, capabilities and opportunities.

Dr. Catherine Bollard is accompanied by her mentees

To Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National, Dr. Bollard is the most deserving mentor for this award. She has provided advice and guidance to over 93 individuals, including 22 junior faculty, 27 post-doctoral fellows and 12 graduate students. Dr. Bollard also acts as a mentor to other senior investigators at Children’s National, particularly those in the Bone Marrow Transplantation division.

“For the past 15 years, Cath has been a strong mentor, friend, advocate, and voice of reason for me and has been instrumental in my success, both at Baylor College of Medicine and now at Children’s National,” said Hanley. “With her support and mentorship, I have been fortunate to publish high impact papers, earn a number of awards and receive prestigious grants. Without her guidance this wouldn’t have been possible.”

Amy Hont, M.D., oncologist for the Center for Cancer and Immunology Research at Children’s National, mentioned that Dr. Bollard is endlessly dedicated to her mentees and staff. “Dr. Bollard has been incredibly supportive of my research career throughout my training and progression to faculty. I feel very fortunate that I have been able to benefit not only from her unparalleled knowledge and expertise, but also her career advice and resources.”

Dr. Bollard leads clinical and research efforts to fight cancer and other inflammatory diseases by strengthening the immune system using adoptive cell therapy. She is a former president of the International Society of Cellular Therapy, and the current president of the Foundation for the Accreditation for Cellular Therapy (FACT). As a distinguished hematologist, immunologist and immunotherapist, she is working to develop cell and gene therapies for patients with cancer, viral infections and immune mediated diseases. She is especially interested in bone marrow and cord blood transplantation and improving outcomes after such transplant by decreasing infectious complications and preventing relapse. Dr. Bollard also has a specific interest in targeting viral infections in immune-suppressed patient populations, including individuals living with the human immunodeficiency virus.

little girl with cancer

Pediatric advance care planning linked to families’ positive caregiving appraisals

little girl with cancer

In a first-of-its-kind clinical trial, experts directly measured families’ appraisals of caregiving as one potential benefit to pediatric advance care planning.

Little is known about how families respond to pediatric advance care planning. Physicians often are concerned that initiating pediatric advance care planning conversations with families is too distressing for them.

But a first-of-its-kind clinical trial led by Maureen E. Lyon, Ph.D., F.A.B.P.P., principal investigator, and Jessica Thompkins, B.S.N, R.N., C.P.N., research nurse coordinator, both at Children’s National Hospital, directly measured families’ appraisals of caregiving as one potential benefit to pediatric advance care planning.

The clinical trial, summarized in a video abstract,  shows that compared to controls, families’ participation in Family-Centered Advance Care Planning for Teens with Cancer (FACE®-TC) resulted in positive appraisals of their caregiving for their child with cancer while not significantly burdening them with distress or strain.

“Clinicians can be assured of the benefit and tolerability of this person-centered/family-supported model of pediatric advance care planning,” Thompkins says.

Families randomized to the FACE®-TC pediatric advance care planning intervention showed significantly greater positive family appraisals of caregiving and overwhelmingly, families reported the experience as worthwhile without adding undue distress or strain, compared to controls.

“This evidence meets practice guidelines for an intervention that could be extended to other adolescents living with serious illnesses and their families,” Dr. Lyon adds.

The clinical trial’s results also showed that FACE®-TC families significantly increased positive caregiving appraisals at three months post-intervention compared to controls. No significant differences were found between groups for strain or distress.

Wilm's Tumor

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

Wilms 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. “Wilms 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.