Antibody Engineered Platelets Attracted by Bacteria-Induced Tumor-Specific Blood Coagulation for Checkpoint Inhibitor Immunotherapy

摘要

Bacteria can act as a promising anti-tumor platform due to their specific targeting capacity to the tumor microenvironment. In this study, it is discovered that intravenous administration of Escherichia coli TOP10 induces rapid and intense blood coagulation in tumor tissues instead of normal tissues. It is demonstrated that E. coli TOP10 can act as an activator of a coagulation cascade to trigger abnormal hemorrhage, blood coagulation, and inflammation with abundant macrophages recruitment in tumors. In addition, the recruited macrophages are principally polarized by lipopolysaccharide in the bacterial wall to the anti-tumor M1-like phenotype. Based on the above finding, coagulation-tropism blood platelets decorated with CD47 antibodies (Anti-CD47), which possess tropism for bacteria-treated tumors are further prepared. As a result, Anti-CD47 blocks the "don't eat me" signal from tumor cells, consequently promoting the phagocytosis of polarized M1-like phenotype macrophages for tumor cells. This manipulation of local blood coagulation in tumors may find great potential for accurately delivering immune checkpoint inhibitors and facilitating tumor immunotherapy.