Anti-Human PD-1 (Dostarlimab)

Human PD-1

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 (RUO). Non-Therapeutic.

2-8° C Wet Ice

This non-therapeutic biosimilar antibody uses the same variable region sequence as the therapeutic antibody Dostarlimab. This product is for research use only. Dostarlimab activity is directed against Human PD-1.

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.

Dostarlimab is a humanized monoclonal antibody that acts as a PD-1 receptor antagonist^{4, 5}. Generated from a mouse hybridoma using SHM-XELTM technology, Dostarlimab was developed for the treatment of various cancers, and in 2021 was approved in the EU and USA for treatment of adult patients with mismatch repair deficient recurrent or advanced endometrial cancer⁴.

Dostarlimab binds to and inhibits PD-1 and potently blocks interaction with PD-L1 and PD-L2, thus restoring immune function by activating T cells^{4, 5}. Dostarlimab also acts as a functional antagonist in a human CD4+ mixed lymphocyte reaction assay, leading to increased IL-2 production.

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-1, CD279

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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. Markham A. Dostarlimab: First Approval. Drugs. 81(10):1213-1219. 2021.
5. https://www.anaptysbio.com/wp-content/uploads/PD1-EORTC-poster-final.pdf