Open AccessNanoparticle-enabled innate immune stimulation activates endogenous tumor-infiltrating T cells with broad antigen specificities
Author(s) -
Qian Yin,
Wei 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,
Yuehhsiu Chien,
Calvin J. Kuo,
Mark M. Davis
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2016168118
Subject(s) - immune system , antigen , cancer immunotherapy , cytotoxic t cell , biology , immunotherapy , cd8 , endogeny , innate immune system , cancer research , immunology , tumor antigen , microbiology and biotechnology , in vitro , biochemistry
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.