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.