融合蛋白
融合
癌症研究
医学
化学
生物化学
基因
哲学
语言学
重组DNA
作者
Sijin Li,Yang Xia,Rui Huang,Qianqian Wang,Xuan Zhang,Zhangchun Guan,Ming‐Shien Wen,Ying Xu,Wei Zhang,Dan Liú,Junnian Zheng,Ming Shi
标识
DOI:10.1016/j.bbadis.2024.167159
摘要
Chimeric antigen receptor T (CAR-T) cell therapy is regarded as a potent immunotherapy and has made significant success in hematologic malignancies by eliciting antigen-specific immune responses. However, response rates of CAR-T cell therapy against solid tumors with immunosuppressive microenvironments remain limited. Co-engineering strategies are advancing methods to overcome immunosuppressive barriers and enhance antitumor responses. Here, we engineered an IL-2 mutein co-engineered CAR-T for the improvement of CAR-T cells against solid tumors and the efficient inhibition of solid tumors. We equipped the CAR-T cells with co-expressing both tumor antigen-targeted CAR and a mutated human interleukin-2 (IL-2 m), conferring enhanced CAR-T cells fitness in vitro, reshaped immune-excluded TME, enhanced CAR-T infiltration in solid tumors, and improved tumor control without significant systemic toxicity. Overall, this subject demonstrates the universal CAR-T cells armed strategy for the development and optimization of CAR-T cells against solid tumors.
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