T Cell Engaging Immunotherapies, Highlighting Chimeric Antigen Receptor (CAR) T Cell Therapy

SIMPLE SUMMARY: The ultimate goal of T cell-engaging immunotherapy is to endorse the activity of a person’s own cytotoxic T cells in the tumor microenvironment, finally destroying cancer cells. Several types of immunotherapy are either approved for use or are under study in clinical trials to determine their effectiveness in treating various types of cancer. Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging in the field and has shown unprecedented success in the treatment of hematological malignancies. It entails the collection of a patient’s T cells to genetically engineer them in the lab to express CARs that target surface antigens on tumors to help identify and eradicate the tumor. However, major issues remain to be solved to enable generalized CART cell therapies in the clinic. Novel approaches to tackle these problems are being developed rapidly and are reviewed in this publication. ABSTRACT: In the past decade, chimeric antigen receptor (CAR) T cell technology has revolutionized cancer immunotherapy. This strategy uses synthetic CARs to redirect the patient’s own immune cells to recognize specific antigens expressed on the surface of tumor cells. The unprecedented success of anti-CD19 CAR T cell therapy against B cell malignancies has resulted in its approval by the US Food and Drug Administration (FDA) in 2017. However, major scientific challenges still remain to be addressed for the broad use of CAR T cell therapy. These include severe toxicities, limited efficacy against solid tumors, and immune suppression in the hostile tumor microenvironment. Furthermore, CAR T cell therapy is a personalized medicine of which the production is time- and resource-intensive, which makes it very expensive. All these factors drive new innovations to engineer more powerful CAR T cells with improved antitumor activity, which are reviewed in this manuscript.