Dual-Responsive Antibody Production and Releasing Platform for Anti-Cancer Immunotherapy

Immune Checkpoint Blockade (ICB) therapies have emerged as a groundbreaking strategy in cancer immunotherapy. Despite their potential, their effectiveness in treating solid tumors is significantly challenged by several factors, including the insufficient accumulation of therapeutic agents and the prevalence of "cold" tumors with limited T-cell infiltration and strong immunosuppressive environments. These factors collectively limit the response rate to ICB therapies. To address these limitations, our study explores the integration of ICB with treatments inducing Immunogenic Cell Death (ICD). ICD plays a crucial role in transforming the tumor microenvironment by releasing damage-associated molecular patterns (DAMPs), which recruit and activate dendritic cells. This process not only aids in presenting tumor antigens to T cells but also boosts the overall anti-tumor immune response, making immunologically "cold" tumors more "hot" and responsive to ICB therapy.<br/><br/>We aimed to use ICD not just to release DAMPs, but as a key to regulate antibody release. We combined photodynamic therapy (PDT), a laser-sensitized method of inducing cell death, with gene delivery techniques to produce antibodies, facilitating the laser-sensitized release of these antibodies. This strategy ensures that the laser-sensitized release of antibodies occurs directly within the tumor microenvironment. Such spatial and temporal precision in antibody release maximizes the therapeutic potential of the antibodies, enhancing their ability to target and neutralize tumor cells effectively. Furthermore, this method minimizes off-target effects and reduces the risk of systemic toxicity, a common concern with conventional immunotherapy approaches. In this study, we successfully demonstrate a novel approach to overcoming the limitations of ICB therapies by developing a laser-activated nanoparticle platform that enhances antibody delivery and immune response through the targeted production and release of anti-PD-L1 antibodies and induction of ICD.