In-situ vaccination immunotherapy of colorectal cancer with STING agonist-integrated supramolecular nanovectors

The immunosuppressive tumor immune microenvironment and low tumor immunogenicity invariably subvert the efficacy of cancer vaccine and the antitumor immunity. An alternative approach to improve cancer vaccination immunotherapy is to synergistically trigger stimulator of interferon genes (STING) activation for transforming immunologically 'cold' tumor into 'hot' tumor. Herein, we presented a supramolecular nanovector (namely HCCSM) integrating with the chemotherapeutic agent camptothecin (CPT) and STING agonist MSA-2 for in-situ vaccination immunotherapy of colorectal cancer. The nanovector was prepared via well-tunable host-guest complexation of cyclodextrin-grafted hyaluronic acid with MSA-2 and adamantine-conjugated prodrug of CPT. Upon intravenous injection, HCCSM achieved active tumor targeting by recognizing highly expressed CD44 on colorectal tumor cells, and specifically co-delivered CPT and MSA-2 into tumors. CPT effectively induced immunogenic cell death (ICD) of tumor cells and triggered tumor-associated antigens (TAAs) release at the tumor site. Subsequently, tumor infiltrating-dendritic cells captured TAAs and MSA-2 to enhance antigen cross-presentation through the activation of STING pathway and secretion of type-I interferon. HCCSM elicited robust antitumor immunity and thus exhibited remarkable therapeutic benefit in primary and distant CT26 colorectal tumors. Our developed nanovector represents an effective combination strategy for vaccination immunotherapy of colorectal cancer.