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PD-L1-Binding antigen presenters: redirecting vaccine-induced antibodies for cancer immunotherapy
This study developed a modular immune-bridging platform—PD-L1-binding antigen presenter (PBAP)—which achieves targeted labeling of PD-L1-positive tumor cells by fusing viral antigens (e.g., varicella-zoster virus gE) or tumor antigens (e.g., HER2 domain IV) with the PD-1 extracellular domain and an Fc fragment. PBAP-gE, combined with gE-specific antibodies induced by the herpes zoster vaccine LZ901, significantly inhibited tumor growth in vitro and in mouse models through NK cell-mediated ADCC. PBAP-HER2 synergized with the clinical antibody Herceptin and the ADC drug Kadcyla to kill HER2-negative, PD-L1-positive tumor cells. The study demonstrated that the antitumor effect primarily relied on vaccine-induced antibodies and NK cells, rather than CD8+ T cells. This platform exhibits tumor type universality and modular potential, offering a new strategy to overcome tumor antigen heterogeneity and immune evasion. The Structural Biology Core Facility provided technical support for negative stain electron microscopy: using a Talos L120C microscope to characterize the morphology of the GE-I53-50 nanoparticle vaccine.
2026/04/24
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