Effects of off-the-shelf allogeneic CAR iNKT

Simonetta F, Lohmeyer JK, Hirai T, et al. Allogeneic CAR-invariant Natural Killer T Cells Exert Potent Antitumor Effects Through Host CD8 T Cell Cross-Priming. Clinical Cancer Research. 2021; (doi: 10.1158/1078-0432.CCR-21-1329).

Researchers report that allogeneic chimeric antigen receptor (CAR)-engineered invariant natural killer T (iNKT) cells generate host CD8 T-cell antitumor responses with a powerful antitumor effect that lasts longer than the allogeneic cells do physically. This cell population does not run the risk of one of the key immunological challenges of off-the-shelf allogeneic CAR T-cell therapies — graft-versus-host-disease induction — and has immunomodulatory properties. The direct antitumor effects of murine CAR iNKT cells were evaluated both in vitro and in vivo. An immunocompetent mouse model of B-cell lymphoma then assessed the relationship between allogeneic CAR iNKT cells and endogenous immune cells. According to the findings, allogeneic CAR iNKT cells produced strong direct and indirect antitumor activity when administered across major histocompatibility complex-barriers by generating tumor-specific antitumor immunity through host CD8 T-cell cross-priming. The results suggest that using off-the-shelf allogeneic CAR iNKT cells could be of significant value in the clinic, the authors conclude.

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