• Stephen J Bagley and Donald M O'Rourke.
• Division of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States; Glioblastoma Translational Center of Excellence, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: Sbagley@pennmedicine.upenn.edu.
• Pharmacol. Ther. 2020 Jan 1; 205: 107419.

AbstractChimeric 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 CAR T cells for solid tumors, as well as an overview of strategies to improve CAR T cell efficacy in non-hematologic malignancies.Copyright © 2019 Elsevier Inc. All rights reserved.

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