期刊
MOLECULAR THERAPY
卷 28, 期 11, 页码 2320-2339出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2020.09.015
关键词
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资金
- National Institutes of Health [R01NS106379]
- Alex's Lemonade Stand Foundation
- Cure4Cam Foundation (ALSF)
- Alliance for Cancer Gene Therapy (ACGT)
- American Lebanese Syrian Associated Charities
Chimeric antigen receptor (CAR) T cell therapy has garnered significant excitement due to its success for hematological malignancies in clinical studies leading to the US Food and Drug Administration (FDA) approval of three CD19-targeted CAR T cell products. In contrast, the clinical experience with CAR T cell therapy for solid tumors and brain tumors has been less encouraging, with only a few patients achieving complete responses. Clinical and preclinical studies have identified multiple roadblocks, including (1) a limited array of targetable antigens and heterogeneous antigen expression, (2) limited T cell fitness and survival before reaching tumor sites, (3) an inability of T cells to efficiently traffic to tumor sites and penetrate physical barriers, and (4) an immunosuppressive tumor microenvironment. Herein, we review these challenges and discuss strategies that investigators have taken to improve the effector function of CAR T cells for the adoptive immunotherapy of solid tumors.
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