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)
Off-the-shelf allogeneic chimeric antigen receptor-engineered T-cell therapies offer new promise, with the discovery that CAR-engineered invariant natural killer T(iNKT) cells trigger powerful antitumor responses. The effect, mediated by host CD8 T-cell cross-priming and observed in an immunocompetent murine model of B-cell lymphoma, is evident even after the physical persistence of transferred allogeneic cells runs out. The durable anti-tumor behavior addresses one major issue challenging off-the-shelf T-cell therapies: limited persistence. The other big obstacle, risk of graft-versus-host disease (GVHD), is immaterial since the CAR iNKT cells are not associated with GVHD induction.