期刊
BLOOD REVIEWS
卷 45, 期 -, 页码 -出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.blre.2020.100695
关键词
CAR T cell therapy; Resistance to CAR T cells; Combination therapy
类别
资金
- Conquer Cancer Foundation
- Margie and Andy Rooke Fund for Leukemia Research
CAR T cell therapy has shown impressive response rates in refractory B-cell malignancies, but faces challenges in solid malignancies. Experimental strategies combining small molecules and monoclonal antibodies are being explored to overcome resistance mechanisms to CAR T cells.
Chimeric antigen receptor (CAR) T cell therapy is currently approved for treatment of refractory B-cell malignancies. Response rates in these diseases are impressive by historical standards, but most patients do not have a durable response and there remains room for improvement. To date, CAR T cell activity has been even more limited in solid malignancies. These limitations are thought to be due to several pathways of resistance to CAR T cells, including cell-intrinsic mechanisms and the immunosuppressive tumor microenvironment. In this review, we discuss current experimental strategies that combine small molecules and monoclonal antibodies with CAR T cells to overcome these resistance mechanisms. We describe the biological rationale, pre-clinical data and clinical trials in progress that test the efficacy and safety of these combinations.
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