Bionic lipoprotein loaded with chloroquine-mediated blocking immune escape improves antitumor immunotherapy

Abstract

Tumor immunotherapy hold great promise for eradicating tumors. However, immune escape and the immunosuppressive microenvironment of tumor usually limit the efficiency of tumor immunotherapy. Therefore, simultaneously blocking immune escape and improving immunosuppressive microenvironment are the current problems to be solved urgently. Among them, CD47 on cancer cells membrane could bind to signal regulatory protein α (SIRPα) on macrophages membrane and sent out “don't eat me” signal, which was an important pathway of immune escape. The large number of M2-type macrophages in tumor microenvironment was a significant factor contributing to the immunosuppressive microenvironment. Here, we present a drug loading system for enhancing cancer immunotherapy, comprising CD47 antibody (aCD47) and chloroquine (CQ) with bionic lipoprotein (BLP) carrier (BLP-CQ-aCD47). On the one hand, as drug delivery carrier, BLP could allow CQ to be preferentially taken up by M2-type macrophages, thereby efficiently polarized M2-type tumor-promoting cells into M1-type anti-tumor cells. On the other hand, blocking CD47 from binding to SIRPα could block the “don't eat me” signal, and improve the phagocytosis of macrophages to tumor cells. Taken together, BLP-CQ-aCD47 could block immune escape, improve immunosuppressive microenvironment of tumor, and induce a strong immune response without substantial systemic toxicity. Therefore, it provides a new idea for tumor immunotherapy.