Liposome-Based Co-Immunotherapy with TLR Agonist and CD47-SIRPa Checkpoint Blockade for Efficient Treatment of Colon Cancer

Antitumor immunity is an essential component of cancer therapy and is primarily mediated by the innate immune response, which plays a critical role in initiating and shaping the adaptive immune response. Emerging evidence has identified innate immune checkpoints and pattern recognition receptors, such as CD47 and Toll-like receptor 7 (TLR7), as promising therapeutic targets for cancer treatment. Based on the fusion protein Fc-CV1, which comprises a high-affinity SIRPa variant (CV1), and the Fc fragment of the human IgG1 antibody, we exploited a preparation which coupled Fc-CV1 to imiquimod (TLR7 agonist)-loaded liposomes (CILPs) to actively target CT26. WT syngeneic colon tumor models. In vitro studies revealed that CILPs exhibited superior sustained release properties and cell uptake efficiency compared to free imiquimod. In vivo assays proved that CILPs exhibited more efficient accumulation in tumors, and a more significant tumor suppression effect than the control groups. This immunotherapy preparation possessed the advantages of low doses and low toxicity. These results demonstrated that a combination of immune checkpoint blockade (ICB) therapy and innate immunity agonists, such as the Fc-CV1 and imiquimod-loaded liposome preparation utilized in this study, could represent a highly effective strategy for tumor therapy.

Automated summary

Antitumor immunity is crucial for cancer therapy and is primarily mediated by innate immune response. CD47 and Toll-like receptor 7 (TLR7) are promising therapeutic targets. A fusion protein called Fc-CV1 and liposomes loaded with imiquimod (TLR7 agonist) were used to target colon tumor models. In vitro and in vivo studies showed that this immunotherapy preparation had superior properties and low toxicity, making it an effective strategy for tumor therapy.