期刊
ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING
卷 13, 期 -, 页码 193-216出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-chembioeng-092120-092914
关键词
chimeric antigen receptor; adoptive cell therapy; CAR-T cell; hypoxia; metabolism; genetic engineering
T cells engineered to express chimeric antigen receptors (CARs) have shown success in treating B-cell malignancies, but effectiveness against solid tumors is limited. Overcoming these challenges requires multidimensional CAR-T cell engineering approaches and a better understanding of the tumor microenvironment.
T cells engineered to express chimeric antigen receptors (CARs) have shown remarkable success in treating B-cell malignancies, reflected by multiple US Food and Drug Administration-approved CAR-T cell products currently on the market. However, various obstacles have thus far limited the use of approved products and constrained the efficacy of CAR-T cell therapy against solid tumors. Overcoming these obstacles will necessitate multidimensional CAR-T cell engineering approaches and better understanding of the intricate tumor microenvironment (TME). Key challenges include treatment-related toxicity, antigen escape and heterogeneity, and the highly immunosuppressive profile of the TME. Notably, the hypoxic and nutrient-deprived nature of the TME severely attenuates CAR-T cell fitness and efficacy, highlighting the need for more sophisticated engineering strategies. In this review, we examine recent advances in protein- and cell-engineering strategies to improve CAR-T cell safety and efficacy, with an emphasis on overcoming immunosuppression induced by tumor metabolism and hypoxia.
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