Nanoparticle-enabled innate immune stimulation activates endogenous tumor-infiltrating T cells with broad antigen specificities
Qian Yin, Wong Yu, Caitlin L. Grzeskowiak, Jing Li, Huang Huang, Jing Guo, Liang Chen, Feng Wang, Fan Zhao, Lotta von Boehmer, Thomas J. Metzner, John T. Leppert, Yueh‐hsiu Chien, Calvin J. Kuo, Mark M. Davis
Abstract
Significance Tumors are often infiltrated by T lymphocytes recognizing either self- or mutated antigens but are generally inactive. Self-specific CD8 + T cells are particular characteristics of tumor types with lower tumor mutation burden and poorer outcomes. Unlike foreign-specific T cells, they have been curiously resistant to stimulation with cognate antigens. We developed an innate immunity-stimulating nanoparticle to activate tumor-infiltrating CD8 + T cells recognizing both self- and neoantigens in a potent yet safe manner. This resulted in effective tumor growth inhibition or elimination in two murine tumor models and the activation of endogenous T cells in patient-derived tumor organoids across three cancer types. This strategy represents a promising pathway for broadly effective cancer immunotherapy.