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MAIT TCR-engineered T cells are an adoptive cell therapy consisting of human T cells genetically modified to express a mucosal-associated invariant T (MAIT) cell receptor. Unlike conventional TCR-T therapies that target peptide antigens presented by polymorphic HLA molecules, these cells recognize the non-polymorphic MHC class I-related molecule (MR1) when it is loaded with riboflavin (vitamin B2) biosynthetic intermediates, such as 5-OP-RU. This HLA-independent recognition mechanism potentially allows for a universal therapeutic approach across diverse patient populations. The therapy's antitumor efficacy is significantly enhanced by the administration of riboflavin pathway metabolites or prodrugs like 5-amino-6-D-ribitylaminouracil (5-A-RU), which prime tumor cells to express MR1 and trigger targeted cytotoxicity. The cells are typically engineered using CRISPR-Cas12-mediated homology-directed repair to ensure precise TCR insertion and endogenous TCR knockout.
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