Programmed death-ligand 1 (PD-L1) and Cluster of Differentiation 47 (CD47) (PD-L1/CD47)

IBI322 is a bispecific antibody that simultaneously targets Programmed death-ligand 1 (PD-L1) and Cluster of Differentiation 47 (CD47). PD-L1 is a transmembrane protein that suppresses the adaptive immune response by binding to PD-1 on T cells, a mechanism frequently exploited by tumor cells to evade immune surveillance [UniProt Q9NZQ7]. CD47 is a widely expressed "don't eat me" signal that interacts with SIRPα on myeloid cells to inhibit phagocytosis, providing a mechanism for innate immune evasion [UniProt Q08722]. By blocking both pathways, IBI322 aims to synergistically enhance anti-tumor activity by activating both T-cell-mediated killing and macrophage-mediated phagocytosis [Innovent Biologics, 2020]. The bispecific design of IBI322 is engineered to prioritize binding to PD-L1-positive tumor cells, which helps mitigate the hematologic toxicities, such as anemia, commonly associated with non-selective CD47 inhibitors that bind to red blood cells [Chen et al., 2021]. This dual-targeting approach is currently being investigated in clinical trials for various advanced solid tumors and hematological malignancies [ClinicalTrials.gov NCT04328831]. The therapeutic goal is to overcome resistance to single-agent checkpoint inhibitors by engaging both the innate and adaptive arms of the immune system.

Other names

CD274B7-H1Integrin-associated proteinIAPMER6OA3

Dual blockade of the PD-1/PD-L1 and CD47/SIRPα signaling pathways to restore T-cell mediated cytotoxicity and enhance macrophage-mediated phagocytosis of tumor cells.