Steven Feins1,2,3, Weimin Kong1,2,3, Erik F. Williams1,2,3, Michael C. Milone4,1,3,5, Joseph A. Fraietta4,1,2,3,5
1Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, Pennsylvania
2Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
3Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
4Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
5Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, Pennsylvania
Tóm tắt
Chimeric antigen receptor (CAR) T‐cell therapy represents a major advancement in personalized cancer treatment. In this strategy, a patient's own T cells are genetically engineered to express a synthetic receptor that binds a tumor antigen. CAR T cells are then expanded for clinical use and infused back into the patient's body to attack and destroy chemotherapy‐resistant cancer. Dramatic clinical responses and high rates of complete remission have been observed in the setting of CAR T‐cell therapy of B‐cell malignancies. This resulted in two recent FDA approvals of CAR T cells directed against the CD19 protein for treatment of acute lymphoblastic leukemia and diffuse large B‐cell lymphoma. Thus, CAR T cells are arguably one of the first successful examples of synthetic biology and personalized cellular cancer therapy to become commercially available. In this review, we introduce the concept of using CAR T cells to break immunological tolerance to tumors, highlight several challenges in the field, discuss the utility of biomarkers in the context of predicting clinical responses, and offer prospects for developing next‐generation CAR T cell‐based approaches that will improve outcome.
