Recombinant cancer nanovaccine for targeting tumor-associated macrophage and remodeling tumor microenvironment

Abstract

The efficient cancer vaccines require the codelivery of potent antigens and highly immunostimulatory adjuvants to the same antigen-presenting cells (APCs) to initiate a robust immune response. In this work, a clinically used trichosanthin served as an adjuvant to prepare a minimalist “all-in-one” vaccine that was a recombinant protein (termed rTL) of trichosanthin and an antigen legumain peptide. rTL was further incorporated into a nanovaccine delivery system (LrTL) using a liposome-encapsulated technology. LrTL can trigger a robust cytotoxic T lymphocytes (CTL) response by activation of APCs that enhance immunostimulatory cytokine secretion (e.g., TNF-α, IL-12, and IFN-γ) and trigger T-cell immunity. By targeting tumor-associated macrophages (TAM), the nanovaccine carried out the anticancer immunity by eliminating TAM and thereby remodeling the tumor microenvironment. Subcutaneous immunization with the nanovaccine yielded a potent anti-tumor activity in several cancer models, including B16-F10, Lewis lung cancer (LLC), intracranial LLC xenograft, as well as CT-26 colon cancer. These findings demonstrate that the nanovaccine is a simple, safe, and robust strategy for cancer immunotherapy. The vaccination strategy offers a general applicability in various cancer types by targeting TAM and remodeling tumor microenvironment.