Summary
Background
This non-therapeutic biosimilar antibody uses the same variable regions as the therapeutic antibody, Sintilimab, making it ideal for research use. Sintilimab is a humanized IgG4 kappa monoclonal antibody with an S228P hinge stabilization mutation that specifically reacts with programmed cell death protein 1 (PD-1), also known as CD279. Sintilimab is shown to have a greater affinity for human PD-1 compared to both nivolumab and pembrolizumab. Sintilimab also shows cross-reactivity to PD-1 cynomolgus monkey species. PD-1 is an inhibitory receptor belonging to the CD28 family of the Ig superfamily, and it is transiently expressed on the cell surface of CD4 and CD8 T cells, B cells, as well as myeloid cells. PD-L1 is the main ligand of PD-1 and is expressed on the surface of tumor cells and antigen-presenting cells (APCs). PD-1 and PD-L1 interactions are central to immune homeostasis and prevention of autoimmunity. PD-1 binding to PD-L1 inhibits T cell activation, thereby diminishing T cell proliferation, cytokine production, and cytotoxic activity. This phenomenon is critical in the downregulation of the immune response during chronic inflammation and minimizing tissue damage. Cancers, such as squamous cell carcinoma, lung cancer, melanoma, ovarian cancer, renal cell carcinoma, colon adenocarcinoma, and breast adenocarcinoma, often express PD-L1 in high abundance, wherein the cancer cells exploit the PD1/PD-L1 pathway to evade immune surveillance via immune evasion. In immune checkpoint inhibitor-responsive experimental models, the tumor growth can be transiently arrested in vivo through treatment with anti-PD-1 antibodies, e.g., sintilimab, which block the interactions between PD-1 and PD-L1 proteins.
