STING-activating & ICD dual-response whole tumor cell vaccine amplifies TNBC immunotherapy.

Abstract

Spatiotemporally-tailored activation of tumor specific immune-response remains a critical challenge for effective whole tumor cell vaccines (TCVs). Herein, we reported a TCV platform obtained by nanoparticle-mediated photo-chemotherapy to generate whole tumor cell vaccine under near-infrared (NIR) laser irradiation. The photo-chemo treatment can trigger the yielded IPL-TCV to activate stimulator of interferon genes (STING) pathways and immunogenic cell death (ICD), which broaden the antigen spectrum of TCV and enhance lymph node (LN) targeted delivery. The combination of TCV with NIR laser irradiation can synergistically activate both innate and adaptive immunity, leading to potent antitumor immune responses that suppress tumor growth. We further demonstrate that IPL-TCV strategy facilitates dendritic cell (DCs) recruitment, maturation, and subsequent T cell activation, which elicits remarkable efficacy in reducing tumor growth, preventing tumor occurrence. This study highlights photo-chemo coordination based personalized TCV strategy to augment cancer immunotherapy by spatiotemporally-tailored innate and adaptive immunity stimulation.