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Vittorio Gallo and Mark Batshaw

Children’s National Research Institute releases annual report

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Vittorio Gallo and Marc Batshaw

Children’s National Research Institute directors Vittorio Gallo, Ph.D., and Mark Batshaw, M.D.

The Children’s National Research Institute recently released its 2019-2020 academic annual report, titled 150 Years Stronger Through Discovery and Care to mark the hospital’s 150th birthday. Not only does the annual report give an overview of the institute’s research and education efforts, but it also gives a peek in to how the institute has mobilized to address the coronavirus pandemic.

“Our inaugural research program in 1947 began with a budget of less than $10,000 for the study of polio — a pressing health problem for Washington’s children at the time and a pandemic that many of us remember from our own childhoods,” says Vittorio Gallo, Ph.D., chief research officer at Children’s National Hospital and scientific director at Children’s National Research Institute. “Today, our research portfolio has grown to more than $75 million, and our 314 research faculty and their staff are dedicated to finding answers to many of the health challenges in childhood.”

Highlights from the Children’s National Research Institute annual report

  • In 2018, Children’s National began construction of its new Research & Innovation Campus (CNRIC) on 12 acres of land transferred by the U.S. Army as part of the decommissioning of the former Walter Reed Army Medical Center campus. In 2020, construction on the CNRIC will be complete, and in 2012, the Children’s National Research Institute will begin to transition to the campus.
  • In late 2019, a team of scientists led by Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, traveled to the Democratic Republic of Congo to collect samples from 60 individuals that will form the basis of a new reference genome data set. The researchers hope their project will generate better reference genome data for diverse populations, starting with those of Central African descent.
  • A gift of $5.7 million received by the Center for Translational Research’s director, Lisa Guay-Woodford, M.D., will reinforce close collaboration between research and clinical care to improve the care and treatment of children with polycystic kidney disease and other inherited renal disorders.
  • The Center for Neuroscience Research’s integration into the infrastructure of Children’s National Hospital has created a unique set of opportunities for scientists and clinicians to work together on pressing problems in children’s health.
  • Children’s National and the National Institute of Allergy and Infectious Diseases are tackling pediatric research across three main areas of mutual interest: primary immune deficiencies, food allergies and post-Lyme disease syndrome. Their shared goal is to conduct clinical and translational research that improves what we know about those conditions and how we care for children who have them.
  • An immunotherapy trial has allowed a little boy to be a kid again. In the two years since he received cellular immunotherapy, Matthew has shown no signs of a returning tumor — the longest span of time he’s been tumor-free since age 3.
  • In the past 6 years, the 104 device projects that came through the National Capital Consortium for Pediatric Device Innovation accelerator program raised $148,680,256 in follow-on funding.
  • Even though he’s watched more than 500 aspiring physicians pass through the Children’s National pediatric residency program, program director Dewesh Agrawal, M.D., still gets teary at every graduation.

Understanding and treating the novel coronavirus (COVID-19)

In a short period of time, Children’s National Research Institute has mobilized its scientists to address COVID-19, focusing on understanding the virus and advancing solutions to ameliorate the impact today and for future generations. Children’s National Research Institute Director Mark Batshaw, M.D., highlighted some of these efforts in the annual report:

  • Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, is looking at whether or not the microbiome of bacteria in the human nasal tract acts as a defensive shield against COVID-19.
  • Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research, and her team are seeing if they can “train” T cells to attack the invading coronavirus.
  • Sarah Mulkey, M.D., Ph.D., an investigator in the Center for Neuroscience Research and the Fetal Medicine Institute, is studying the effects of, and possible interventions for, coronavirus on the developing brain.

You can view the entire Children’s National Research Institute academic annual report online.

Vote for STAT Madness

It’s a three-peat! Children’s National again competes in STAT Madness

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Vote for STAT Madness

Children’s National Hospital collects patients’ blood, extracts T-cells and replicates them in the presence of specific proteins found on cancer cells which, in essence, teaches the T-cells to target specific tumor markers. Training the T-cells, growing them to sufficient quantities and ensuring they are safe for administration takes weeks. But when patients return to the outpatient clinic, their T-cell infusion lasts just a few minutes.

For the third consecutive year, Children’s National was selected to compete in STAT Madness, an annual bracket-style competition that chooses the year’s most impactful biomedical innovation by popular vote. Children’s entry, “Immunotherapy of relapsed and refractory solid tumors with ex vivo expanded multi-tumor associated antigen specific cytotoxic T lymphocytes,” uses the body’s own immune system to attack and eliminate cancer cells in pediatric and adult patients with solid tumor malignancies.

In 2018, Children’s first-ever STAT Madness entry advanced through five brackets in the national competition and, in the championship round, finished second. That innovation, which enables more timely diagnoses of rare diseases and common genetic disorders, helping to improve kids’ health outcomes around the world, also was among four “Editor’s Pick” finalists, entries that spanned a diverse range of scientific disciplines.

An estimated 11,000 new cases of pediatric cancer were diagnosed in children 14 and younger in the U.S. in 2019. And, when it comes to disease, cancer remains the leading cause of death among children, according to the National Institutes of Health. An enterprising research team led by Children’s National faculty leveraged T-cells – essential players in the body’s immune system – to treat pediatric and adult patients with relapsed or refractory solid tumors who had exhausted all other therapeutic options.

“We’re using the patient’s own immune system to fight their cancer, rather than more traditional chemotherapy drugs,” says Catherine M. Bollard, M.D., director of the Center for Cancer & Immunology Research at Children’s National and co-senior author of the study. “It’s more targeted and less toxic to the patient. These T-cells home in on any cancer cells that might be in the body, allowing healthy cells to continue to grow,” Dr. Bollard adds.

That means patients treated in the Phase I, first-in-human trial didn’t lose their hair and weren’t hospitalized for the treatment. After a quick clinical visit for their treatment, they returned to normal activities, like school, with good energy levels.

“With our specially trained T-cell therapy, many patients who previously had rapidly progressing disease experienced prolonged disease stabilization,” says Holly J. Meany, M.D., a Children’s National oncologist and the study’s co-senior author. “Patients treated at the highest dose level showed the best clinical outcomes, with a six-month, progression-free survival of 73% after tumor-associated antigen cytotoxic T-cell (TAA-T) infusion, compared with 38% with their immediate prior therapy.”

The multi-institutional team published their findings from the study online July 29, 2019, in the Journal of Clinical Oncology.

“Our research team and our parents are delighted that some patients treated in our study continue to do well following T-cell therapy without additional treatment. In some cases, two years after treatment, patients do not appear to have active disease and are maintaining an excellent quality of life,” says Amy B. Hont, M.D., the study’s lead author. “One of these was a patient whose parents were told his only other option was palliative care. Our innovation gives these families new hope,” Dr. Hont adds.

The 2020 STAT Madness #Core64 bracket opened March 2, and the champion will be announced April 6.

In addition to Drs. Hont, Meany and Bollard, Children’s National co-authors include C. Russell Cruz, M.D., Ph.D., Robert Ulrey, MS, Barbara O’Brien, BS, Maja Stanojevic, M.D., Anushree Datar, MS, Shuroug Albihani, MS, Devin Saunders, BA, Ryo Hanajiri, M.D., Ph.D., Karuna Panchapakesan, MS, Payal Banerjee, MS, Maria Fernanda Fortiz, BS, Fahmida Hoq, MBBS, MS, Haili Lang, M.D., Yunfei Wang, DrPH, Patrick J. Hanley, Ph.D., and Jeffrey S. Dome, M.D., Ph.D.; and Sam Darko, MS, National Institute of Allergy and Infectious Diseases.

Financial support for the research described in this post was provided by the Children’s National Hospital Heroes Gala, Alex’s Army Foundation, the Children’s National Board of Visitors and Hyundai Hope on Wheels Young Investigator Grant to Support Pediatric Cancer Research, the Children’s National Research Institute Bioinformatics Unit, the Clinical and Translational Science Institute and the National Institutes of Health under award No. UL1-TR001876.

t-cells

Tailored T-cell therapies neutralize viruses that threaten kids with PID

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t-cells

Tailored T-cells specially designed to combat a half dozen viruses are safe and may be effective in preventing and treating multiple viral infections, according to research led by Children’s National Hospital faculty.

Catherine Bollard, M.B.Ch.B., M.D., director of the Center for Cancer and Immunology Research at Children’s National and the study’s senior author, presented the teams’ findings Nov. 8, 2019, during a second-annual symposium jointly held by Children’s National and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Children’s National and NIAID formed a research partnership in 2017 to develop and conduct collaborative clinical research studies focused on young children with allergic, immunologic, infectious and inflammatory diseases. Each year, they co-host a symposium to exchange their latest research findings.

According to the NIH, more than 200 forms of primary immune deficiency diseases impact about 500,000 people in the U.S. These rare, genetic diseases so impair the person’s immune system that they experience repeated and sometimes rare infections that can be life threatening. After a hematopoietic stem cell transplantation, brand new stem cells can rebuild the person’s missing or impaired immune system. However, during the window in which the immune system rebuilds, patients can be vulnerable to a host of viral infections.

Because viral infections can be controlled by T-cells, the body’s infection-fighting white blood cells, the Children’s National first-in-humans Phase 1 dose escalation trial aimed to determine the safety of T-cells with antiviral activity against a half dozen opportunistic viruses: adenovirus, BK virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human Herpesvirus 6 and human parainfluenza-3 (HPIV3).

Eight patients received the hexa-valent, virus-specific T-cells after their stem cell transplants:

  • Three patients were treated for active CMV, and the T-cells resolved their viremia.
  • Two patients treated for active BK virus had complete symptom resolution, while one had hemorrhagic cystitis resolved but had fluctuating viral loads in their blood and urine.
  • Of two patients treated prophylactically, one developed EBV viremia that was treated with rituximab.

Two additional patients received the T-cell treatments under expanded access for emergency treatment, one for disseminated adenoviremia and the other for HPIV3 pneumonia. While these critically ill patients had partial clinical improvement, they were being treated with steroids which may have dampened their antiviral responses.

“These preliminary results show that hexaviral-specific, virus-specific T-cells are safe and may be effective in preventing and treating multiple viral infections,” says Michael Keller, M.D., a pediatric immunologist at Children’s National and the lead study author. “Of note, enzyme-linked immune absorbent spot assays showed evidence of antiviral T-cell activity by three months post infusion in three of four patients who could be evaluated and expansion was detectable in two patients.”

In addition to Drs. Bollard and Keller, additional study authors include Katherine Harris M.D.; Patrick J. Hanley Ph.D., assistant research professor in the Center for Cancer and Immunology; Allistair Abraham, M.D., a blood and marrow transplantation specialist; Blachy J. Dávila Saldaña, M.D., Division of Blood and Marrow Transplantation; Nan Zhang Ph.D.; Gelina Sani BS; Haili Lang MS; Richard Childs M.D.; and Richard Jones M.D.

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Children’s National-NIAID 2019 symposium presentations

“Welcome and introduction”
H. Clifford Lane, M.D., director of NIAID’s Division of Clinical Research

“Lessons and benefits from collaboration between the NIH and a free-standing children’s hospital”
Marshall L. Summar, M.D., director, Rare Disease Institute, Children’s National

“The hereditary disorders of PropionylCoA and Cobalamin Metabolism – past, present and future”
Charles P. Venditti, M.D., Ph.D., National Human Genome Research Institute Collaboration

“The road(s) to genetic precision therapeutics in pediatric neuromuscular disease: opportunities and challenges”
Carsten G. Bönnemann, M.D., National Institute of Neurological Disorders and Stroke

“Genomic diagnostics in immunologic diseases”
Helen Su, M.D., Ph.D., National Institute of Allergy and Infectious Diseases

“Update on outcomes of gene therapy clinical trials for X-SCID and X-CGD and plans for future trials”
Harry Malech, M.D., National Institute of Allergy and Infectious Diseases

“Virus-specific T-cell therapies: broadening applicability for PID patients”
Catherine Bollard, M.D., Children’s National 

“Using genetic testing to guide therapeutic decisions in Primary Immune Deficiency Disease”
Vanessa Bundy, M.D., Ph.D., Children’s National 

Panel discussion moderated by Lisa M. Guay-Woodford, M.D.
Drs. Su, Malech, Bollard and Bundy
Morgan Similuk, S.C.M., NIAID
Maren Chamorro, Parent Advocate

“Underlying mechanisms of pediatric food allergy: focus on B cells
Adora Lin, M.D., Ph.D., Children’s National 

“Pediatric Lyme outcomes study – interim update”
Roberta L. DeBiasi, M.D., MS, Children’s National 

“Molecular drivers and opportunities in neuroimmune conditions of pediatric onset”
Elizabeth Wells, M.D., Children’s National 

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Also read: Johan’s story
View: Safeguarding Johan’s future

Newborn baby laying in crib

Can cells collected from bone marrow stimulate generation of new neurons in babies with CHD?

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Newborn baby laying in crib

The goal of the study will be to optimize brain development in babies with congenital heart disease (CHD) who sometimes demonstrate delay in the development of cognitive and motor skills.

An upcoming clinical trial at Children’s National Hospital will harness cardiopulmonary bypass as a delivery mechanism for a novel intervention designed to stimulate brain growth and repair in children who undergo cardiac surgery for congenital heart disease (CHD).

The NIH has awarded Children’s National $2.5 million to test the hypothesis that mesenchymal stromal cells (MSCs), which have been shown to possess regenerative properties and the ability to modulate immune responses in a variety of diseases, collected from allogeneic bone marrow, may promote regeneration of damaged neuronal and glial cells in the early postnatal brain. If successful, the trial will determine the safety of the proposed treatment in humans and set the stage for a Phase 2 efficacy trial of what could potentially be the first treatment for delays in brain development that happen before birth as a consequence of congenital heart disease. The study is a single-center collaboration between three Children’s National physician-researchers: Richard Jonas, M.D., Catherine Bollard, M.B.Ch.B., M.D. and Nobuyuki Ishibashi, M.D.

Dr. Jonas, chief of cardiac surgery at Children’s National, will outline the trial and its aims on Monday, November 18, 2019, at the American Heart Association’s Scientific Sessions 2019. Dr. Jonas was recently recognized by the Cardiac Neurodevelopmental Outcome Collaborative for his lifelong research of how cardiac surgery impacts brain growth and development in children with CHD.

Read more about the study: Researchers receive $2.5M grant to optimize brain development in babies with CHD.

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Regenerative Cell Therapy in Congenital Heart Disease – Protecting the Immature Brain
Presented by Richard Jonas, M.D.
AHA Scientific Sessions
Session CH.CVS.608 Congenital Heart Disease and Pediatric Cardiology Seminar: A Personalized Approach to Heart Disease in Children
9:50 a.m. to 10:05 a.m.
November 18, 2019

Catherine Bollard named to Medicine Maker’s Annual Power List

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Catherine Bollard

Children’s National Health System’s Chief of Allergy and Immunology, Catherine Bollard M.D., has been named to The Medicine Maker’s 2017 Power List, which honors the top 100 most influential people in the world of drug development. Dr. Bollard is featured as a ”Champion of Change,” a category that highlights experts striving to make the world a better place by getting medicines to those who need them the most. She joins notable scientists Frances Collins, director of the U.S. National Institutes of Health, and Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases.

In the Medicine Maker feature, Dr. Bollard describes the inspiration behind her dedication to cellular immunotherapy and how that led to her team’s breakthrough T-cell therapy that gives complete remissions in over 50 percent of some patient groups. Read the full piece here.