Enhanced Antigen Capture via Cholinephosphate-Mediated Cell Membrane Interactions to Improve In Situ Tumor Vaccines.

Abstract

Inadequate antigen capture and insufficient antigen-presenting cell (APC) activity at tumor sites limit the effectiveness of in situ vaccines. To address this, poly(glutamic acid-cholinephosphate) (pGluCP) is introduced as a polymer with cell membrane adhesion properties capable of capturing both water-soluble and insoluble membrane antigens from necrotic tumor cells while recruiting more APCs. The approach uses manganese-mineralized black phosphorus (MnBP) coated with pGluCP and αPD-1 antibodies to create the MnBP@pGluCP-αPD-1 complex for in situ vaccines. MnBP eradicates tumor cells via photothermal effects, releasing antigens, while Mn²⁺ ions activate the intracellular STING pathway, acting as an adjuvant. pGluCP captures these antigens, forming pathogen-mimicking micro-nanoparticles, leading to an in situ vaccine (MnBP@pGluCP/antigens) that co-localizes antigens and adjuvants. The αPD-1 antibody alleviates tumor-induced immune suppression, enhancing tumor cell-specific killing. This study demonstrates the potential of leveraging cholinephosphate-cell membrane interactions to improve antigen presentation efficiency, significantly bolstering the efficacy of in situ tumor vaccines and opening new avenues for advanced cancer immunotherapy.