Systemic nano-delivery of low-dose STING agonist targeted to CD103+dendritic cells for cancer 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 evalu-ated 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. 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 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.

Automated summary

In this study, a systemically administered CD103+ dendritic cell (DCs) targeted liposomal formulation was developed, which enhanced anti-tumor immune response and reduced off-target toxicities by targeted delivery of CDNs. The results showed significant anti-tumor efficacy of the liposomal formulation at low dose.