Potentiating Novel Engineered Cellular Therapies for Solid Tumors
Marcela V. Maus, MD, PhD
In preliminary data from the first-in-human clinical trial of CART-EGFRvIII in patients with recurrent GBM expressing EGFRvIII, Dr. Maus’ group found that infusion of CART-EGFRvIII cells is safe, without evidence of off-tumor toxicity such as cross-reactivity to wild type EGFR. Although they observed trafficking of CAR T cells into the brain tumor, and loss of EGFRvIII expression, they noted that residual tumor retained high levels of expression of EGFR (wild-type and other non-EGFRvIII mutations), and that there was a large influx of new T cell immigrants which were not CAR T cells, and could in fact be part of the immunosuppressive microenvironment observed in GBM. Thus, Dr. Maus has set out to design next-generation CAR T cells to address these two findings. They have been designing and testing CART-EGFRvIII cells that include a second transgene that enables them to target wild-type EGFR in situ, or to reverse the inhibitory tumor microenvironment.
Dr. Maus is board-certified in Internal Medicine, Medical Oncology and in Hematology, with particular clinical training in melanoma, myeloma, and bone marrow transplant. She is the Director of Cellular Immunotherapy at the Massachusetts General Hospital Cancer Center and an Attending Physician in the Bone Marrow Transplant and Cell Therapy division of Oncology at the Massachusetts General Hospital. She is an Assistant Professor at Harvard Medical School, an Associate Member of the Broad Institute of Harvard and MIT, and an Associate Member of the Ragon Institute of MGH, MIT, and Harvard.