Targeting and Specific Activation of Antigen-Presenting Cells by Endogenous Antigen-Loaded Nanoparticles Elicits Tumor-Specific Immunity

Adv Sci (Weinh). 2019 Nov 8;7(1):1900069. doi: 10.1002/advs.201900069. eCollection 2020 Jan.

Abstract

Immunotherapy has shown tremendous promise for improving cancer treatment. Unfortunately, antigen-presenting cells (APCs) in cancer patients cannot effectively recognize and process tumor antigens to activate host immune responses. In this study, an approach is developed to improve cancer immunotherapy that utilizes endogenous antigen-carrying nanoparticles (EAC-NPs), which encompasses a set of antigens isolated from solid tumors and adjuvants. The EAC-NPs specifically target APCs and subsequently result in enhanced T cell responses and improved antitumor efficacy. Mechanistic studies reveal that the EAC-NPs enhance and prolong the presence of immune compounds in APCs, which ensure persistent antigen loading and stimulation, induce a rapid proliferation of CD4+ and CD8+ T cells, and significantly increase the ratios of intratumoral CD4+ T/Treg and CD8+ T/Treg. The work using nanotechnology provides a promising strategy in improving antitumor immunity by enhancing the immunogenicity and presentation of tumor self-antigens for cancer immunotherapy.

Keywords: CD8+/CD4+ T cells; HSP70‐chaperoned polypeptides; antigen‐presenting cells; cancer immunotherapy; codelivery system.