Neoantigen Immunotherapeutic-Gel Combined with TIM-3 Blockade Effectively Restrains Orthotopic Hepatocellular Carcinoma Progression

Herein, we integrate the Hepa1-6 liver cancer-specific neoantigen, toll-like receptor 9 agonist and stimulator of interferon genes agonist by silk-hydrogel package, and combine with TIM-3 blockade to elicit robust antitumor immunity for effectively suppressing orthotopic hepatocellular carcinoma (HCC) progression. Unlike intradermal injection of simple mixed components with short-term immune protection, the neoantigen immunotherapeutic-gels evoke long-term immune protection to achieve significant prophylactic and therapeutic activity against HCC through only one-shot administration without any side effects. Notably, the synergized immunotherapy by further combining NGC-gels with TIM-3 antibody significantly reduces regulatory T-cells and increases the IFN-gamma and IL-12p70 levels in tumor tissues for promoting the infiltration of IFN-gamma+CD8+T-cells and 41BB+CD8+T-cells to achieve complete remission (4/7) and prevent pulmonary metastasis in orthotopic HCC, and establish long-term memory against tumor rechallenge with remarkably longer survival time (180 days). Overall, this study provides an attractive and promising synergistic strategy for HCC immunotherapy with possible clinical translation prospects.

Automated summary

This study combines various therapeutic approaches, such as liver cancer-specific neoantigen, immune agonists, and TIM-3 blockade, using a silk-hydrogel package to effectively treat and provide long-term immune protection against orthotopic hepatocellular carcinoma (HCC). The synergistic immunotherapy significantly reduces tumor growth, prevents metastasis, and establishes long-term memory against tumor rechallenge.