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• W4288717962 abstract "Abstract Engineering immune cells with chimeric antigen receptors (CAR) 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. Here we devised an approach to program a non-classical 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, CAR-MAIT cells exhibit high levels of cytotoxicity towards 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, which is a conserved compound that activates MAIT cells through MHC-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 . Key Points MAIT cells expressing CARs effectively kill CD19 and Her2 expressing targets CAR-MAITs display strong cytotoxicity with lower TNF-γ compared to CD8+ CAR-T cells" @default.
• W4288717962 created "2022-07-30" @default.
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• W4288717962 date "2022-07-28" @default.
• W4288717962 modified "2023-09-23" @default.
• W4288717962 title "Engineering human Mucosal Associated Invariant T (MAIT) cells with chimeric antigen receptors for cancer immunotherapy¹" @default.
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• W4288717962 doi "https://doi.org/10.1101/2022.07.28.501764" @default.
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