SU2C Scientific Research Teams
SU2C-St. Baldrick’s Pediatric Cancer Dream Team: Immunogenomics to Create New Therapies for High-Risk Childhood Cancers
John M. Maris, M.D.
Giulio D'Angio Endowed Professor of Pediatrics in the Perelman School of Medicine, University of Pennsylvania; Director, Center for Childhood Cancer Research at the Children’s Hospital of Philadelphia
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Crystal L. Mackall, M.D.
Chief of Pediatric Oncology Branch, Head of Immunology Section of the National Cancer Institute (NCI)
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“In the past 20 years, very few new therapies have been developed for pediatric cancer. This Dream Team has deep expertise in each of the most lethal pediatric cancers and includes thought leaders in the fields of genomics and immunotherapeutics. It is our goal, indeed our expectation, that we will initiate a sustained effort to maximize pediatric cancer cure rates through a genomics-anchored immunotherapeutic program.”— John M. Maris, M.D.
Curative chemotherapy for cancer was first realized in children, and survival rates for many childhood cancers improved dramatically through the latter quarter of the 20th century. However, those cure rates have plateaued since the 1990s, and for some childhood cancers, there have been little to no improvements. In addition, standard therapies are exceedingly toxic, leaving childhood cancer survivors with life-threatening illnesses and often leading to side effects that reduce the quality of life for young patients as they grow into adulthood. Although the understanding of the biology of childhood cancer has advanced substantially in the past two decades, new precision therapies have not yet significantly improved childhood cancer outcomes.
Compared to adult tumors, genetic mutations that can be targeted with currently available small molecules are rare in pediatric cancers. This suggests that pediatric oncology research must move beyond traditional methods of identifying treatments in order to substantially improve outcomes. Immunotherapeutics are treatments that employ the body’s own immune system against disease. Immunotherapeutics targeting cell surface molecules have shown impressive results in early pediatric clinical trials, supporting the notion that they could become an important new tool against childhood cancers. Continuing advances will require the combined efforts of genomics research to identify new targets and immunotherapeutics research to exploit these targets.
The Stand Up To Cancer-St. Baldrick’s Pediatric Dream Team led by Maris and Mackall will bring together world-class researchers in two highly impactful disciplines, genomics and immunotherapeutics, to establish a collaborative, scientifically rigorous, multidisciplinary program to develop novel, targeted immunotherapeutics for childhood cancers that are among the most challenging to cure. The aim of this project is to establish the foundation for a sustained effort to maximize pediatric cancer cure rates through a genomics-anchored immunotherapeutic program.
To test their idea, the Dream Team, which comprises some of the best pediatric cancer researchers and clinicians in the world, have devised a three-pronged approach to focus on childhood cancers that inflict the highest burden of mortality and morbidity. They will first identify and validate cancer-specific, cell-surface molecules that could serve as potential targets for immunotherapy of high-risk pediatric cancers. Armed with this knowledge, they will then develop various immunotherapeutics that recognize and kill cancer cells expressing these molecules. Examples of potential immunotherapeutics include specific antibodies, immunotoxins and engineered immune cells called chimeric-antigen receptor T cells or CAR T cells. Finally, the Dream Team plans to conduct pivotal first-in-child immunotherapeutic trials with the most promising of these agents.
The interactive and complementary specific aims to be pursued here will lead to novel therapies that have the potential to dramatically improve outcomes for some of the most lethal childhood cancers.
Watch a short video in which the SU2C-St. Baldrick’s Pediatric Cancer Dream Team leaders Maris and Mackall talk more about the science behind their project: