An Intracellular Gelated Macrophage-Based Vaccine for Tumor Immunotherapy.

Abstract

Cancer vaccines represent a promising approach for tumor immunotherapy. It requires effective tumor antigen delivery, specific antigen recognition, and the induction of a strong and durable immune response. Inspired by recent advances in hydrogel-based vaccine systems and growing research leveraging adoptive cells as therapeutic agents, a strategy of constructing intracellular gelated macrophage (GM)-based vaccines has been proposed. Proinflammatory macrophages were introduced as cellular therapeutics and hydrogelated through direct intracellular permeation of poly(ethylene glycol) diacrylate (PEGDA) monomers and UV-initiated radical polymerization to trap a large number of tumor antigens and immune adjuvants (GMAGs). The GMAGs could accumulate in both tumor tissues and tumor-draining lymph nodes, forming favorable immunization spots to continuously codeliver antigens and adjuvants, recruit dendritic cells for antigen presentation, and prime T cell activation. In murine breast cancer and melanoma models, the GMAGs were able to induce strong and durable immunity, inhibit tumor progression, and extend the overall survival. This strategy synergistically inherits the targeting ability and biocompatibility of macrophages alongside the drug-loading and sustained-release properties of hydrogels, representing a promising and multifunctional approach to cancer vaccines.