工程化 NK 外泌体原位捕获抗原用于增强肿瘤免疫治疗

Natural killer (NK) cells are widely involved in the field of tumor immunotherapy due to their unique killing ability.

However, the durability and efficacy of NK-cell monotherapy are facing great challenges owing to the limitation of immunosuppressive tumor microenvironment (TME). NK cell-derived exosomes (Neo) not only play an innate immunomodulatory role similar to NK cells but also emerge as promising antitumor nanocarriers.

In this study, an engineered Neo (R@Neo-MN) was designed that encapsulates the multifunctional antitumor drug (Raddeanin a, RA) and modified with maleimide (Mal, M) and mannose (Man, N). The obtained R@Neo-MN could not only exert NK cell-like antitumor function but also induce the immunogenic cell death of tumors to release tumor-associated antigens (TAAs).

Furthermore, R@Neo-MN activated the cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) to release type I interferons (IFN). Then, R@Neo-MN could capture TAAs through Mal and specifically target dendritic cells (DCs) through Man, thereby promoting the maturation of DCs and enhancing tumor-specific cytotoxic T-cell (CTL)-mediated adaptive immunity. The released IFN further promoted the infiltration and activition of NK cells and CTLs at the tumor site.

Our study suggested a novel strategy that harnesses both innate and adaptive immunity for enhanced tumor immunotherapy.