InVivoSIM anti-human PD-1 (Tislelizumab Biosimilar)

About InVivoSIM anti-human PD-1 (Tislelizumab Biosimilar)

This non-therapeutic biosimilar antibody uses the same variable regions from the therapeutic antibody Tislelizumab making it ideal for research use. This Tislelizumab biosimilar reacts with human PD-1 (programmed death-1) also known as CD279. PD-1 is a 50-55 kDa cell surface receptor encoded by the Pdcd1 gene that belongs to the CD28 family of the Ig superfamily. PD-1 is transiently expressed on CD4 and CD8 thymocytes as well as activated T and B lymphocytes and myeloid cells. PD-1 expression declines after successful elimination of antigen. Additionally, Pdcd1 mRNA is expressed in developing B lymphocytes during the pro-B-cell stage. PD-1’s structure includes a ITIM (immunoreceptor tyrosine-based inhibitory motif) suggesting that PD-1 negatively regulates TCR signals. PD-1 signals via binding its two ligands, PD-L1 and PD-L2 both members of the B7 family. Upon ligand binding, PD-1 signaling inhibits T-cell activation, leading to reduced proliferation, cytokine production, and T-cell death. Additionally, PD-1 is known to play key roles in peripheral tolerance and prevention of autoimmune disease. Induced PD-L1 expression is common in many tumors including squamous cell carcinoma, colon adenocarcinoma, and breast adenocarcinoma. PD-L1 overexpression results in increased resistance of tumor cells to CD8 T cell mediated lysis. PD-L1 overexpression results in increased resistance of tumor cells to CD8 T cell mediated lysis. In experimental models of melanoma, tumor growth can be transiently arrested via treatment with antibodies which block the interaction between PD-L1 and its receptor PD-1. The structure of Tislelizumab has been modified to maximally inhibit the binding of PD-1 to PD-L1 and minimize the binding of Tislelizumab to Fcγ receptors. The epitope of Tislelizumab is formed on the CC′ loop of the front β sheet face of PD-1, which is innovative among anti-PD-1 antibodies; in comparison, other PD-1 antibodies, like Nivolumab and Pembrolizumab, bind to the N-terminal region and the C’D loop of PD-1, respectively. Tislelizumab is able to bind to human PD-1 with high specificity and affinity, with the disassociation constant being 0.15 nmol/L. At the 5 mg/kg dose, PD-1 receptor occupancy is >90%. In clinical studies, Tislelizumab has shown preliminary anti-tumor effects in various solid tumors.