Synergistic anti-tumor efficacy of a hollow mesoporous silica-based cancer vaccine and an immune checkpoint inhibitor at the local site

Immune checkpoint inhibitors elicit durable tumor regression in multiple types of tumor, but may induce potential side effects with low response rates in many tumors. Herein, to increase the therapeutic efficacy of immune checkpoint inhibitors, a hollow mesoporous silica (HMS) nanosphere-based cancer vaccine was combined with an immune checkpoint inhibitor, anti-programmed death-ligand 1 (anti-PD-L1) antibody. The HMS nanospheres function as adjuvants that promote dendritic cell activation and antigen cross-presentation. Mice immunized with the HMS-based cancer vaccine show suppressed tumor growth with increased tumor necrosis factor- alpha (TNF- alpha), interleukin-1 beta (IL-1 beta), and interleukin-2 (IL-2) levels in their spleens compared with those without HMS-based cancer vaccine. Moreover, the HMS-based cancer vaccine synergistically acts with the anti-PD-L1 antibody on the tumor. The combination of an HMSbased cancer vaccine and an antibody markedly decreases the required dose of the immune checkpoint inhibitor. Mice locally administered with the HMS-based cancer vaccine and 1/8 dose of a standard antiPD-L1 antibody (25 mu g/mouse) show comparable anti-tumor effect and significantly increased CD4 + and CD8 + T cell populations, compared with those systemically immunized with the standard anti-PD-L1 antibody done at 200 mu g/mouse. Our work presents a promising cancer treatment strategy of combining an immune checkpoint inhibitor with an HMS-based cancer vaccine.

Automated summary

In this study, a combination therapy of an immune checkpoint inhibitor and an HMS-based cancer vaccine was proposed to enhance the therapeutic efficacy of the immune checkpoint inhibitor. The HMS-based cancer vaccine acts as an adjuvant to activate dendritic cells and present antigens. The results showed that the combination therapy reduced the required dose of the immune checkpoint inhibitor and increased the anti-tumor effect, along with increased CD4+ and CD8+ T cell populations.