Tumor-draining lymph node targeting chitosan micelles as antigen-capturing adjuvants for personalized immunotherapy

Abstract

Tumor-draining lymph node (TDLN), already bathed in tumor antigens, has been proposed as an intriguing site for cancer immunotherapy. Targeted delivery of adjuvants to TDLN, presumably could induce antitumor immunity for personalized immunotherapy. Although molecular adjuvants can be used for personalized immunotherapy, their efficacy is limited by insufficient antigen uptake by dendritic cells (DCs). In contrast, nanomaterial-based adjuvants can enhance antigen uptake by DCs by capturing antigens. Herein, mannose modified stearic acid-grafted chitosan micelles (MChSA), which presumably could target TDLN, were engineered to capture endogenous antigens and enhance antigen uptake by DCs for personalized immunotherapy. MChSA micelles showed strong antigen-capturing and TDLN targeting ability. Importantly, MChSA micelles induced robust CD4⁺ and CD8⁺ T cell responses, stimulated antitumor related cytokine secretion and notably inhibited tumor growth. MChSA micelles, which can target TDLN to induce potent antitumor immune responses as antigen-capturing adjuvants, exhibit great potential in personalized cancer immunotherapy.

Keywords: Antigen-capturing; Chitosan micelles; Personalized immunotherapy; Tumor-draining lymph node targeting; adjuvants.