Anti-Human PD-1 (Toripalimab) (P801-GRP)

PD-1 is a transmembrane protein in the CD28/CTLA-4 subfamily of the Ig superfamily1,2. When stimulated via the T cell receptor (TCR), Tregs translocate PD-1 to the cell surface3. 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 ligands1. 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 cells3. PD-1 is an immune checkpoint receptor that suppresses cancer-specific immune responses4. 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 glycolysis2. 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 immunotherapy2. JS-001 (Toripalimab) is a recombinant, humanized monoclonal antibody that binds to PD-1, thereby inhibiting binding of ligands PD-L1 and PD-L2 to PD-14,5. In activated human peripheral blood mononuclear cell (PBMC)-derived T cells, Toripalimab binding induces internalization of the PD-1 receptor, resulting in decreased PD-1 on the cell membrane, and also increased human T cell proliferation and interferon-γ and TNF-α secretion5. In cynomolgus monkey models, PD-1+/CD4 + and PD-1+/CD8+ cells decrease after blockade4. The efficacy of Toripalimab immunotherapy has been tested in melanoma, urothelial carcinoma, renal cell carcinoma 6 , and nasopharyngeal carcinoma subjects7. Toripalimab is also known as TAB0015. Toripalimab combines the murine complementary- determining regions of a human PD-1 antibody with optimized human framework regions. A S228P substitution minimizes Fab arm exchange of the IgG4 molecule. Toripalimab does not cross-react with mouse or woodchuck PD-14.