Anti-Human PD-1 (Toripalimab)

Unknown

This biosimilar antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Recombinant biosimilar antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

To protect mouse colonies from infection by pathogens and to assure that experimental preclinical data is not affected by such pathogens, all of Leinco’s recombinant biosimilar antibodies are tested and guaranteed to be negative for all pathogens in the IDEXX IMPACT I Mouse Profile.

Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

This non-therapeutic biosimilar antibody uses the same variable region sequence asthe therapeutic antibody Toripalimab. JS-001 (Toripalimab) activity is directed against humanand cynomolgus monkey PD-1. This product is research use only.

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 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-1^4,5. 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.

PD-1 is expressed on activated T cells, B cells, a subset of thymocytes, macrophages, dendritic cells, and some tumor cells and is also retained in the intracellular compartments of regulatory T cells (Tregs).

PD-L1 (CD274; B7H1) and PD-L2 (CD273; B7DC)

1 Matsumoto K, Inoue H, Nakano T, et al. J Immunol. 172(4):2530-2541. 2004.
2 Zhao Y, Harrison DL, Song Y, et al. Cell Rep. 24(2):379-390.e6. 2018.
3 Raimondi G, Shufesky WJ, Tokita D, et al. J Immunol. 176(5):2808-2816. 2006.
4 Fu J, Wang F, Dong LH, et al. Acta Pharmacol Sin. 38(5):710-718. 2017.
5 Keam SJ. Drugs. 79(5):573-578. 2019.
6 Tang B, Yan X, Sheng X, et al. J Hematol Oncol. 12(1):7. 2019.
7 Mai HQ, Chen QY, Chen D, et al. JAMA. 330(20):1961-1970. 2023.