Project Description

Dr. Wang, City of Hope

Dr. Leo Wang
Translational Research Grant
– Solid Tumors/Immunotherapy

Beckman Research Institute of the City of Hope

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Fine Tuning Chimeric Antigen Receptor T Cells For Pediatric Brain Tumors

Dr. Wang’s research is offering great hope to children facing aggressive pediatric brain tumors.  Presently these patients have a very poor prognosis, and for many of these diseases cure rates have not increased in many decades. In fact, brainstem gliomas such as DIPG have no long-term survivors, and most children survive only about 9 months after diagnosis. Clearly, new and better therapies are needed for these conditions. Chimeric Antigen Receptor (CAR) T cells are immune cells that have been reprogrammed to seek and destroy cancer cells. This revolutionary therapy has had an enormous impact on the treatment of leukemia and lymphoma. As a pediatric oncologist, Dr. Wang is committed to bringing this groundbreaking new treatment to pediatric brain tumor patients.

City of Hope has developed CAR T cells that target aggressive brain tumors, and we recently showed that these cells can cause regression of multiply relapsed, metastatic brain tumor lesions in an adult patient. Building on those impressive results, he is working with investigators at City of Hope and Children’s Hospital of Los Angeles to bring this much-needed treatment to pediatric brain tumor patients.

Simultaneously, Dr. Wang’s research laboratory is working to improve CAR T cell therapy for pediatric brain tumors so that it will work in more patients. One major challenge with the current therapy is that the CAR T cells disappear quickly from the brain tumor. Discovering how to keep CAR T cells present and active for longer will make this treatment much more effective, and will also make it easier to manufacture and deliver this therapy to patients. Thus, unlocking these secrets will lead to long-term cures in patients with aggressive brain tumors.

To reach this goal, the team at Beckman Research Institue of the City of Hope proudly states, “We actively engaged in developing new methods for improving CAR T cell persistence. Almost all cellular functions are effected by proteins, so understanding the protein-level changes that drive CAR T cell persistence is critical. However, because we do not know beforehand which protein pathways to focus on, we need to develop comprehensive strategies to evaluate the global protein landscape as it changes in these cells. The best (and only) way to do this, currently, is to use mass spectrometry-based proteomic analysis, a particular expertise of my laboratory. We have previously shown that mass spectrometry can discover new protein pathways that are important for complex cellular processes in blood cells, and expect that application of this innovative discovery platform will permit identification of new targets in CAR T cell persistence. Once we identify these protein pathways, we will prove their importance by manipulating them in the cell culture and mouse brain tumor models we have developed, and then use that information to design better, more effective CAR T cells.”

The Pediatric Cancer Research Foundation is directing funds to further this promising research that gives hope to families facing aggressive brain tumor diagnosis.

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