Clinical investigation of CAR T cells for solid tumors: Lessons learned and future directions

Chimeric antigen receptor (CAR) T cells are a form of autologous immunotherapy that has changed the therapeutic landscape of hematologic malignancies. CAR T cell therapy involves collection of a patient's T cells by apheresis, ex vivo genetic modification of the T cells to encode a synthetic receptor that binds a specific tumor antigen, and infusion of the T cells back into the patient. With the unprecedented success of CAR T cells in leukemia and lymphoma, a growing number of preclinical studies and clinical trials have focused on translating this treatment to solid tumors. In non-hematologic malignancies, however, response rates have been much less favorable. Some of the most significant challenges for CAR T cell immunotherapy in solid cancers include a paucity of unique tumor target antigens, limited CAR T cell trafficking to tumor sites, tumor heterogeneity and antigen loss, and the severely immunosuppressive tumor microenvironment. This review article provides an update on completed and ongoing clinical trials of CART cells for solid tumors, as well as an overview of strategies to improve CART cell efficacy in non-hematologic malignancies. (C) 2019 Elsevier Inc. All rights reserved.