Endolysosomal-Escape Nanovaccines through Adjuvant-Induced Tumor Antigen Assembly for Enhanced Effector CD8 + T Cell Activation

Small. 2018 Apr;14(15):e1703539. doi: 10.1002/smll.201703539. Epub 2018 Mar 1.

Abstract

The activation of tumor-specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight-forward strategy of adjuvant-induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed. The resulting functionalizable nanovaccines are equipped with a pH (low) insertion peptide (pHLIP) to facilitate endolysosomal escape and to promote cytoplasmic localization, with the aim to enhance cross-presentation of the antigen by dendritic cells to effectively activate CD8+ T cell. The results demonstrate that pHLIP-functionalized model nanovaccine can induce endolysosomal escape and enhance CD8+ T cell activation both in vitro and in vivo. Furthermore, based on the adjuvant-induced antigen assembly, nanovaccines of the clinically relevant tumor-associated antigen NY-ESO-1 are generated and show excellent capacity to elicit NY-ESO-1-specific CD8+ T cell activation, demonstrating a high potential of this functionalizable nanovaccine formulation strategy for clinical applications.

Keywords: T cell activation; antigen/adjuvant codelivery; cancer nanovaccines; cross-presentation; endolysosomal escape.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cancer Vaccines / immunology*
  • Cell Line
  • Humans
  • Kinetics
  • Lymphocyte Activation / physiology
  • Polyphenols / chemistry

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Polyphenols