Allogeneic CAR-invariant Natural Killer T Cells Exert Potent Antitumor Effects Through Host CD8 T cell Cross-Priming

Simonetta, F.; Lohmeyer, J. K.; Hirai, T.; Maas-Bauer, K.; Alvarez, M.; Wenokur, A. S.; Baker, J.; Aalipour, A.; Ji, X.; Haile, S.; Mackall, C. L.; Negrin, R. S.

doi:10.1101/2021.02.03.428987

bioRxiv · 10.1101/2021.02.03.428987

Allogeneic CAR-invariant Natural Killer T Cells Exert Potent Antitumor Effects Through Host CD8 T cell Cross-Priming

Simonetta, F.·Lohmeyer, J. K.·Hirai, T.·Maas-Bauer, K.·Alvarez, M.·Wenokur, A. S.·Baker, J.·Aalipour, A.·Ji, X.·Haile, S.·Mackall, C. L.·Negrin, R. S.

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Abstract

The development of allogeneic chimeric antigen receptor (CAR) T cell therapies for off-the-shelf use is a major goal yet faces two main immunological challenges, namely the risk of graft-versus-host-disease (GvHD) induction by the transferred cells and the rejection by the host immune system limiting their persistence. We demonstrate that allogeneic CAR-engineered invariant natural killer T (iNKT) cells, a cell population without GvHD-induction potential that displays immunomodulatory properties, exerted potent direct and indirect antitumor activity in murine models of B-cell lymphoma when administered across major MHC-barriers. In addition to their known direct cytotoxic effect, allogeneic CAR iNKT cells induced tumor-specific antitumor immunity through host CD8 T cell cross-priming, resulting in a potent antitumor effect lasting longer than the physical persistence of the allogeneic cells. The utilization of off-the-shelf allogeneic CAR iNKT cells could meet significant unmet needs in the clinic.

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Simonetta, F., Lohmeyer, J. K., Hirai, T., Maas-Bauer, K., Alvarez, M., Wenokur, A. S., Baker, J., Aalipour, A., Ji, X., Haile, S., Mackall, C. L., Negrin, R. S.. 2021-02-03. Allogeneic CAR-invariant Natural Killer T Cells Exert Potent Antitumor Effects Through Host CD8 T cell Cross-Priming. https://doi.org/10.1101/2021.02.03.428987

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