Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity.

ABSTRACT: CD47, an immune checkpoint receptor frequently unregulated in various blood and solid tumors, interacts with ligand SIPRα on innate immune cells, and conveys a "do not eat me" signal to inhibit macrophage-mediated tumor phagocytosis. This makes CD47 a valuable target for cancer immunotherapy. However, the therapeutic utility of CD47-SIRPα blockade monoclonal antibodies is largely compromised due to significant red blood cell (RBCs) toxicities and fast target-mediated clearance as a result of extensive expression of CD47 on normal cells. To overcome these limitations and further improve therapeutic efficacy, we designed IBI322, a CD47/PD-L1 bispecific antibody which attenuated CD47 activity in monovalent binding and blocked PD-L1 activity in bivalent binding. IBI322 selectively bound to CD4

SUBMITTER: Wang Y 

PROVIDER: S-EPMC10991320 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature