Genetically Reprogrammed Exosomes for Targeted Prostate Cancer Immunotherapy

As one of top leading cancer deaths in men worldwide, prostate cancer (PCa) remains difficult to cure, underscoring unmet medical needs for innovative treatment options. Exosomes are cell-derived membranous vesicles. They play key roles in cell-to-cell communication and have attracted remarkable interest in drug delivery and development. In this study, we exploited a genetic approach to display both anti-human prostate-specific membrane antigen (PSMA) and anti-human CD3 antibodies on exosomal surface. Through simultaneously targeting T cells and PCa tumors, the resulting prostate cancer immunotherapeutic exosomes (PRO Exos) were designed to induce robust anti-cancer cellular immunity. In vitro and in vivo studies demonstrate potent T-cell mediated cytotoxicity specifically against PSMA-expressing PCa cells. Our findings highlight the potential of genetically reprogrammed exosomes for targeted PCa immunotherapy, representing a promising approach for battling PCa. STATEMENT OF SIGNIFICANCE: This work reports the development of genetically reprogrammed exosomes as an immunotherapeutic approach to prostate cancer. Through genetic display of two distinct types of monoclonal antibodies on exosomal surfaces, exosomes were created to simultaneously engage with human T cells and prostate cancer cells to elicit potent anti-tumor immunity. As a potentially general platform, the immunotherapeutic exosomes provide a strategy with promising efficacy and safety profiles for fighting prostate cancer by inducing host immune responses.