PD-1 was first identified in mice, where its expression is induced in the thymus when anti-CD3 antibodies are injected, leading to apoptosis of thymocytes . The human homolog of the PD-1 gene was identified in 1994, sharing 60% sequence homology with the mouse PD-1 protein . PD-1 is expressed in various types of tumors, including melanomas, and plays a significant role in anti-tumor immunity .
The preparation of mouse anti-human PD-1 antibodies involves immunizing mice with human PD-1 protein or peptides. The immune response generates antibodies specific to human PD-1, which can be harvested and purified from the mice. These antibodies are then characterized for their specificity and affinity to human PD-1.
Industrial production of mouse anti-human PD-1 antibodies typically involves the use of hybridoma technology. This process includes:
The interaction between PD-1 and its ligands, PD-L1 and PD-L2, involves specific binding sites on the proteins. Upon ligand binding, PD-1 undergoes phosphorylation within its immunoreceptor tyrosine-based switch motif (ITSM), leading to the recruitment of protein tyrosine phosphatases such as PTPN11/SHP-2 . This recruitment results in the dephosphorylation of key signaling molecules, thereby inhibiting T-cell activation .
PD-1/PD-L1 blocking antibodies, such as those used in cancer immunotherapy, have shown profound clinical activity across diverse cancer types . These antibodies work by preventing the interaction between PD-1 and its ligands, thereby enhancing T-cell activation and promoting anti-tumor immunity .