{"doi":"10.1101/2022.07.28.501764","title":"Engineering human Mucosal Associated Invariant T (MAIT) cells with chimeric antigen receptors for cancer immunotherapy <sup>1</sup>","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","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301631,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":992748,"name":"Ece Karhan","orcid":"0000-0002-4474-965X","position":1,"is_corresponding":false},{"id":318388,"name":"Lina Kozhaya","orcid":"0000-0002-1559-2278","position":2,"is_corresponding":false},{"id":318387,"name":"Lindsey Placek","orcid":"0000-0002-4952-4222","position":3,"is_corresponding":false},{"id":418267,"name":"Qingrong Chen","orcid":"0000-0003-1325-6147","position":4,"is_corresponding":false},{"id":552615,"name":"Mesut Yiğit","orcid":"0000-0002-1179-1253","position":5,"is_corresponding":false},{"id":235097,"name":"Derya Unutmaz","orcid":"0000-0001-8898-6633","position":6,"is_corresponding":false},{"id":318386,"name":"Mikail Dogan","orcid":"0000-0001-8725-9151","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T00:32:02.193874Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}