Anti-Human PD-1 (Sintilimab) (IVMB0535)

PD-1 is a transmembrane protein in the CD28/CTLA-4 subfamily of the Ig superfamily ^1,2. When stimulated via the T cell receptor (TCR), Tregs translocate PD-1 to the cell surface ³. Programmed cell death 1 ligand 1 (PD-L1; CD274; B7H1) and programmed cell death 1 ligand 2 (PD-L2; CD273; B7DC) have been identified as PD-1 ligands ¹. PD-1 is co-expressed with PD-L1 on tumor cells and tumor-infiltrating antigen-presenting cells (APCs) ². Additionally, PD-1 is co-expressed with IL2RA on activated CD4+ T cells ³.

PD-1 is an immune checkpoint receptor that suppresses cancer-specific immune responses ⁴. Additionally, PD-1 acts as a T cell inhibitory receptor and plays a critical role in peripheral tolerance induction and autoimmune disease prevention as well as important roles in the survival of dendritic cells, macrophage phagocytosis, and tumor cell glycolysis ². PD-1 prevents uncontrolled T cell activity, leading to attenuation of T cell proliferation, cytokine production, and cytolytic activities. Additionally, the PD-1 pathway is a major mechanism of tumor immune evasion, and, as such, PD-1 is a target of cancer immunotherapy ².

Sintilimab is a fully human monoclonal antibody that helps restore the endogenous antitumor T cell response by binding to PD-1 on activated T cells and blocking PD-1 from interacting with PD-L1 and PD-L2 ⁵. Sintilimab’s interaction with PD-1 depends on the hydrophobic and aromatic amino acid residues in its complementarity-determining region ⁶. Sintilimab rapidly occupies PD-1 receptors on the surface of CD3+ T cells in peripheral blood and relies on antibody-dependent cell cytotoxicity as its mechanism of action ⁵. Sintilimab is also known as IBI-308 and its chemical name is anti-(human programmed cell death protein 1) (human monoclonal IBI308 gamma4-chain), disulphide with human monoclonal IBI308 kappa-chain, dimer. Sintilimab was generated by yeast display technology ⁷.