CAR-T cell therapy: current limitations and potential strategies

被引:1710
作者
Sterner, Robert C. [1 ]
Sterner, Rosalie M. [2 ]
机构
[1] Univ Wisconsin, Sch Med, Med Scientist Training Program, Madison, WI USA
[2] Mayo Clin, Dept Surg, Rochester, MN 55902 USA
关键词
CHIMERIC ANTIGEN RECEPTOR; PERITONEAL OVARIAN-TUMORS; NON-HODGKIN-LYMPHOMA; CYTOKINE RELEASE; ANTITUMOR EFFICACY; ADOPTIVE IMMUNOTHERAPY; CHECKPOINT BLOCKADE; REGIONAL DELIVERY; SPACER DOMAIN; CD19;
D O I
10.1038/s41408-021-00459-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.
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页数:11
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