Mucosal-associated invariant T cells for cancer immunotherapy

Yan-Ruide Li; Kuangyi Zhou; Matthew Wilson; Adam Kramer; Yichen Zhu; Niels Dawson; Lili Yang

doi:10.1016/j.ymthe.2022.11.019

Mucosal-associated invariant T cells for cancer immunotherapy

Mol Ther. 2023 Mar 1;31(3):631-646. doi: 10.1016/j.ymthe.2022.11.019. Epub 2022 Dec 5.

Authors

Yan-Ruide Li¹, Kuangyi Zhou¹, Matthew Wilson¹, Adam Kramer¹, Yichen Zhu¹, Niels Dawson¹, Lili Yang²

Affiliations

¹ Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: liliyang@ucla.edu.

Abstract

Human mucosal-associated invariant T (MAIT) cells are characterized by their expression of an invariant TCR α chain Vα7.2-Jα33/Jα20/Jα12 paired with a restricted TCR β chain. MAIT cells recognize microbial peptides presented by the highly conserved MHC class I-like molecule MR1 and bridge the innate and acquired immune systems to mediate augmented immune responses. Upon activation, MAIT cells rapidly proliferate, produce a variety of cytokines and cytotoxic molecules, and trigger efficient antitumor immunity. Administration of a representative MAIT cell ligand 5-OP-RU effectively activates MAIT cells and enhances their antitumor capacity. In this review, we introduce MAIT cell biology and their importance in antitumor immunity, summarize the current development of peripheral blood mononuclear cell-derived and stem cell-derived MAIT cell products for cancer treatment, and discuss the potential of genetic engineering of MAIT cells for off-the-shelf cancer immunotherapy.

Keywords: CAR engineering; GvHD; MAIT cell; allogeneic cell therapy; cancer immunotherapy; chimeric antigen receptor engineering; combination therapy; graft-versus-host disease; mucosal-associated invariant T cell; off-the-shelf; stem cell engineering.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Histocompatibility Antigens Class I / chemistry
Histocompatibility Antigens Class I / metabolism
Humans
Immunotherapy
Leukocytes, Mononuclear / metabolism
Mucosal-Associated Invariant T Cells* / metabolism
Neoplasms* / therapy
Receptors, Antigen, T-Cell / genetics

Substances

Receptors, Antigen, T-Cell
Histocompatibility Antigens Class I

Grants and funding

P30 CA016042/CA/NCI NIH HHS/United States