In Situ Manipulation of Dendritic Cells by an Autophagy-Regulative Nanoactivator Enables Effective Cancer Immunotherapy

ACS Nano. 2019 Jul 23;13(7):7568-7577. doi: 10.1021/acsnano.9b00143. Epub 2019 Jul 5.

Abstract

Cellular immunotherapeutics aim to employ immune cells as anticancer agents. Ex vivo engineering of dendritic cells (DCs), the initial role of an immune response, benefits tumor elimination by boosting specific antitumor responses. However, directly activating DCs in vivo is less efficient and therefore quite challenging. Here, we designed a nanoactivator that manufactures DCs through autophagy upregulating in vivo directly, which lead to a high-efficiency antigen presention of DCs and antigen-specific T cells generation. The nanoactivator significantly enhances tumor antigen cross-presentation and subsequent T cell priming. Consequently, in vivo experiments show that the nanoactivators successfully reduce tumor growth and prolong murine survival. Taken together, these results indicate in situ DCs manipulation by autophagy induction is a promising strategy for antigen presentation enhancement and tumor elimination.

Keywords: antigen presentation; autophagy; cancer immunotherapy; dendritic cell; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Autophagy / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • Female
  • Immunotherapy*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Particle Size
  • Surface Properties
  • T-Lymphocytes / immunology