Data from Activating Mucosal-Associated Invariant T Cells Induces a Broad Antitumor Response

• DOI: 10.1158/2326-6066.c.6550414.v1
• Publication Date: 2023-04-04T19:39:06Z
• Authors: Benjamin Ruf; Vanessa V. Catania; Simon Wabitsch; Chi Ma; Laurence P. Diggs; Qianfei Zhang; Bernd Heinrich; Varun Subramanyam; Linda L. Cui; Marie Pouzolles; Christine N. Evans; Raj Chari; Shunsuke Sakai; Sangmi Oh; Clifton E. Barry; Daniel L. Barber; Tim F. Greten

<div>Abstract<p>Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like that recognize non-peptide antigens including riboflavin derivates. Although <i>in vitro</i>–activated MAIT show antitumor activity, the vivo</i> role of in cancer is still unclear. Here, we have shown function when activated by a combination synthetic synthesis pathway–derived antigen 5-OP-RU [5-(2-oxopropylideneamino)-6-D-ribitylaminouracil] and Toll-like receptor 9 (TLR9) agonist CpG. Coadministration CpG induced strong systemic expansion activation with high CD69 expression, pronounced effector memory phenotype, upregulated levels molecules IFNγ, granzyme B, perforin. Activated expanded MAITs potent broad immune response murine models liver metastasis hepatocellular carcinoma, lung metastasis, subcutaneous tumors two different mouse strains. Such tumor inhibition was absent MAIT-deficient <i>Mr1</i><sup>−/−</sup> mice. CRISPR/Cas9-mediated MR1 knockout did not affect efficacy this MAIT-directed immunotherapy, pointing toward an indirect mechanism action. Our findings suggest attractive target for immunotherapy.</p><p><i>See related Spotlight Lantz, p. 996</i>.</p></div>