Targeted delivery of low-dose liposomal STING agonist to CD103+ dendritic cells in tumor immunotherapy

Current methods of STING activation based on intra-tumoral injections of cyclic dinucleotides (CDNs) are not suitable for addressing tumor heterogeneity or for inaccessible, metastatic and abscopal tumors. In this study, we developed systemically administered CD103+ dendritic cell (DCs) targeted liposomal formulations and evaluated the anti-tumor efficacy with low dose. Liposomal CDN formulations were prepared using Clec9a targeting peptide and evaluated therapeutic efficacy in vitro and in vivo in subcutaneous MC38 and B16F10 tumor models and in orthotopic ID8-VEGF ovarian cancer tumor model. Targeted delivery of CDNs is expected to enhance anti-tumor immune response as well as reduce off-target toxicities. With intravenous 0.1 mg/kg or 0.03 mg/kg intraperitoneal systemic CDN dose of the targeted liposomal formulation, our results showed robust immune response with significant antitumor efficacy both as a monotherapy and in combination with anti-PD-L1 antibody. These results show that a CD103+ DC targeted CDN formulation can lead to potent immune stimulation upon systemic administration even in relatively "cold" tumors such as B16F10.--Author's abstract