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Engineering Human MAIT Cells with Chimeric Antigen Receptors for Cancer Immunotherapy.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2022 Oct 15; Vol. 209 (8), pp. 1523-1531. Date of Electronic Publication: 2022 Sep 07. - Publication Year :
- 2022
-
Abstract
- Engineering immune cells with chimeric Ag receptors (CARs) is a promising technology in cancer immunotherapy. Besides classical cytotoxic CD8 <superscript>+</superscript> T cells, innate cell types such as NK cells have also been used to generate CAR-T or CAR-NK cells. In this study, we devised an approach to program a nonclassical 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 <superscript>+</superscript> T cells, expanded them in vitro, and compared their cytotoxicity against tumor cell targets. We show upon activation through CARs that CAR-MAIT cells exhibit high levels of cytotoxicity toward target cells, comparable to CD8 <superscript>+</superscript> CAR-T cells, but interestingly expressed lower levels of IFN-γ than conventional CAR CD8 <superscript>+</superscript> T cells. Additionally, in the presence of vitamin B <subscript>2</subscript> metabolite 5-ARU (5-amino-4-d-ribitylaminouracil dihydrochloride), which is a conserved compound that activates MAIT cells through MHC class 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.<br /> (Copyright © 2022 by The American Association of Immunologists, Inc.)
- Subjects :
- Antigens metabolism
CD8-Positive T-Lymphocytes
Female
Histocompatibility Antigens Class I
Humans
Immunotherapy
Minor Histocompatibility Antigens genetics
Receptors, Antigen, T-Cell
Vitamins
Breast Neoplasms therapy
Lymphoma, B-Cell
Mucosal-Associated Invariant T Cells
Receptors, Chimeric Antigen
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 209
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 36165183
- Full Text :
- https://doi.org/10.4049/jimmunol.2100856