Affiliation:
1. State Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 China
2. Department of Hematology State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 China
3. Frontiers Medical Center Tianfu Jincheng Laboratory Chengdu 610212 China
Abstract
AbstractClinical trials of Chimeric Antigen Receptor T‐cell (CAR‐T) therapy have demonstrated remarkable success in treating both solid tumors and hematological malignancies. Nanobodies (Nbs) have emerged as promising antigen‐targeting domains for CARs, owing to their high specificity, robust stability, and strong affinity, leading to significant advancements in the field of Nb‐CAR‐T. In the realm of T‐cell acute lymphoblastic leukemia (T‐ALL) targets, CD5 stands out as a potentially excellent candidate for T‐cell‐based CAR therapy, due to its distinct expression on the surface of malignant T‐ALL cells. To mitigate graft‐versus‐host disease associated with allogeneic CAR‐T, γδT cells are selected and stimulated from peripheral blood mononuclear cells, and γδT cells are engineered via CRISPR/Cas9 to eliminate fratricide, enabling the creation of fratricide‐resistant CAR‐γδTCD5− cells. In vitro transcribed (IVT) mRNA is used to construct CAR‐T, presenting a safer, faster, and cost‐effective method compared to traditional viral vector approaches. In this study, a CD5‐VHH library is constructed, and specific CD5‐nanobodies are screened for subsequent use in CD5‐CAR‐γδTCD5− therapy. IVT‐mRNA‐CD5‐CAR‐γδTCD5− cells exhibited favorable functional characteristics and demonstrated antitumor efficacy against malignant T cell lines, underlining the potential for advancing mRNA‐CD5‐CAR‐γδTCD5− therapy.
Funder
National Natural Science Foundation of China
Sichuan University
National Key Research and Development Program of China
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献