Developing the next generation of cell therapies through international collaboration

Children’s National Hospital has developed tumor-antigen specific T-cell therapies that have shown success in pre-clinical models and in early phase clinical trials for pediatric patients with solid tumors. Now this promising area of research has earned a major boost from a Cancer Grand Challenges award, supported by two of the largest funders of cancer research in the world — Cancer Research UK and the National Cancer Institute in the U.S.

This award supported the foundation of NexTGen — a team of scientists and clinician researchers with expertise in immunology, proteomics, mathematics and more, across eight institutions in the U.S., U.K. and France. Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, and Martin Pule, M.D., clinical associate professor at the University College of London are the co-leads of this effort.

The NexTGen team is one of four Cancer Grand Challenges teams, representing a total investment of $100 million awarded to diverse, global teams to take on some of the toughest challenges in cancer research. NexTGen will create a new approach that performs clinical and basic research together to facilitate real-time knowledge exchange from the lab to the clinic and back again.

While the more widely known CAR T-cells have made tremendous progress for patients with B-cell leukemias, lymphomas and other blood cancers, the CAR T-cell field has not made the same impact on adult and pediatric solid tumors.

“A tumor cell is very clever because it tries to hide from the immune system by deleting or down-regulating targets that the T-cell is directed towards. Our NexTGen Team is committed to developing a 'next generation T-cell' therapy that will overcome these tumor-induced immune evasion strategies," said Dr. Bollard.

The Cancer Grand Challenges NexTGen team will be working to develop these next-generation cell therapies specifically for children with solid cancers. Cancer is a leading cause of death by disease in children worldwide. Although survival has increased for some pediatric cancers, such as blood cancers, survival for advanced stage and relapsed/refractory pediatric solid tumors has seen little improvement for more than 30 years. The team hopes to build a much deeper understanding of childhood solid tumors and develop and optimize novel therapies for children with these cancers, ultimately improving survival and diminishing the lifelong toxicities often experienced by survivors.

“With our Cancer Grand Challenge, we hope to bring next-generation CAR T-cell therapies to the routine care of children with solid tumors,” said Dr. Bollard. “What excites me most is the energized, passionate group of people we’ve brought together to take this challenge on. Big problems remain to be addressed, but we believe they can be solved, and that we’re the team to solve them."

The NexTGen team unites scientists and clinicians from around the world. The Children’s National investigators who will participate are:

• Nitin Agrawal, Ph.D., associate professor in the Center for Cancer and Immunology Research at Children’s National.
• Conrad Russell Cruz, M.D., Ph.D., principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies at Children’s National.
• Patrick Hanley, Ph.D., chief and director of the cellular therapy program at Children’s National and leader of the Good Manufacturing Practices laboratory.
• Amy Hont, M.D., oncologist in the Center for Cancer and Immunology Research at Children’s National.
• AeRang Kim, M.D., oncologist in the Center for Cancer and Blood Disorders at Children’s National.
• Holly Meany, M.D., oncologist in the Center for Cancer and Blood Disorders at Children’s National.
• Anqing Zhang, Ph.D., biostatistician in the Biostatistics and Study Methodology Department at Children’s National.
• Fahmida Hoq, M.D., program director of clinical research at Children’s National.

The NexTGen team is co-funded by Cancer Research UK, the National Cancer Institute and The Mark Foundation for Cancer Research.

Cancer Grand Challenges supports a global community of diverse, world-class research teams with awards of $25 million to come together, think differently and take on cancer’s toughest challenges. These are the obstacles that continue to impede progress and no one scientist, institution or country will be able to solve them alone. Cancer Grand Challenges teams are empowered to rise above the traditional boundaries of geography and discipline.

Founded by the two largest funders of cancer research in the world, Cancer Grand Challenges aims to make the progress against cancer we urgently need. Cancer Grand Challenges currently supports more than 700 researchers and advocates across 10 countries, representing 11 teams that are supported to take on 10 of the toughest challenges in cancer research.