Engineered Platelet for In Situ Natural Killer Cell Activation to Inhibit Tumor Recurrence.

ABSTRACT

Natural killer (NK) cells offer profound advantages against tumor recurrence due to their unique immunological behavior. NK cell therapies associated with the antibody-dependent cell-mediated cytotoxicity (ADCC) effect have made remarkable progress while being limited by insufficient antibody binding and the exhausted state of NK cells in the postsurgical immunosuppressive microenvironment. Leveraging the adherence of PLT to tumor cells, we developed an exogenously implanted platelet (PLT)-based NK cell-driven system (PLT-IgG-IL15) to improve the identifiability of residual tumors with IgG antibody labeling for NK cells catching and engaging, which consequently restored the ADCC effect and promoted the recovery of their killing function. Furthermore, interleukin-15 (IL-15) participated in the augmentation of NK cell function. Collectively, PLT-IgG-IL15 served as an NK cell tumor cell engager as well as an NK cell charger, achieving a <40% recurrence rate in mouse tumor models.