细胞毒性T细胞
嵌合抗原受体
癌症免疫疗法
CD8型
白细胞介素21
癌细胞
免疫疗法
生物
癌症研究
自然杀伤性T细胞
T细胞
抗原
癌症
免疫学
化学
免疫系统
体外
生物化学
遗传学
作者
Mikail Dogan,Ece Karhan,Lina Kozhaya,Lindsey Placek,Xin Chen,Mesut Yigit,Derya Unutmaz
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2022-10-15
卷期号:209 (8): 1523-1531
被引量:12
标识
DOI:10.4049/jimmunol.2100856
摘要
Abstract Engineering immune cells with chimeric Ag receptors (CARs) is a promising technology in cancer immunotherapy. Besides classical cytotoxic CD8+ T cells, innate cell types such as NK cells have also been used to generate CAR-T or CAR-NK cells. In this study, we devised an approach to program a nonclassical cytotoxic T cell subset called mucosal-associated invariant T (MAIT) cells into effective CAR-T cells against B cell lymphoma and breast cancer cells. Accordingly, we expressed anti-CD19 and anti-Her2 CARs in activated primary human MAIT cells and CD8+ T cells, expanded them in vitro, and compared their cytotoxicity against tumor cell targets. We show upon activation through CARs that CAR-MAIT cells exhibit high levels of cytotoxicity toward target cells, comparable to CD8+ CAR-T cells, but interestingly expressed lower levels of IFN-γ than conventional CAR CD8+ T cells. Additionally, in the presence of vitamin B2 metabolite 5-ARU (5-amino-4-d-ribitylaminouracil dihydrochloride), which is a conserved compound that activates MAIT cells through MHC class I–related (MR1) protein, MAIT cells killed MR1-expressing target breast cancer and B cell lymphoma cell lines in a dose-dependent manner. Thus, MAIT cells can be genetically edited as CAR-T cells or mobilized and expanded by MR1 ligands as an off-the-shelf novel approach to cell-based cancer immunotherapy strategies while being comparable to conventional methods in effectivity.
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