Fig. 1: Biomimetic nanovaccine-mediated IL-15 self-transpresentation in a multivalent form can improve the efficacy and avoid the side effects of IL-15.

a Schematic representation describing the stepwise fabrication of biNV-IL-15. (1) Adenovirus vectors were genetically modified with IL-15/IL-15Rα gene. (2) Recombinant adenovirus transduced the BMDCs to express membrane-bound IL-15 on the cell surface. (3) Tumor antigen priming and DC maturation. (4) The isolation of biNV-IL-15. b Schematic representation depicting the hypothesis of the research: biNV-IL-15 induces the ultrahigh activation of tumor-specific CTLs. Conventional IL-15 treatment has a high probability of binding to nontumor-specific T cells with a large population in the lymph node, resulting in unsatisfactory therapeutic efficacy and serious side effects. On the contrary, biNV-IL-15 would target tumor-specific T cells and simultaneously deliver multivalent IL-15 and tumor antigen to exclusively stimulate tumor-specific T cell activation, improving therapeutic efficacy and preventing side effects. c biNV-IL-15 treatment is more efficacious in tumor-specific T cell activation than IL-15 and biNV co-administration. The T cells have a high possibility to interact with either IL-15 or tumor antigen as well as a low possibility to interact with both IL-15 and tumor antigen through co-administration, leading to inefficient tumor-specific CTL production. By contrast, biNV-IL-15 has a high possibility to simultaneously provide IL-15 and tumor antigen to T cells, resulting in efficient tumor-specific CTL stimulation.