<i>In Situ</i> Manipulation of Dendritic Cells by an Autophagy-Regulative Nanoactivator Enables Effective Cancer Immunotherapy.

Abstract

Cellular immunotherapeutics aim to employ immune cells as anticancer agents. <i>Ex vivo</i> engineering of dendritic cells (DCs), the initial role of an immune response, benefits tumor elimination by boosting specific antitumor responses. However, directly activating DCs <i>in vivo</i> is less efficient and therefore quite challenging. Here, we designed a nanoactivator that manufactures DCs through autophagy upregulating <i>in vivo</i> 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, <i>in vivo</i> experiments show that the nanoactivators successfully reduce tumor growth and prolong murine survival. Taken together, these results indicate <i>in situ</i> DCs manipulation by autophagy induction is a promising strategy for antigen presentation enhancement and tumor elimination.