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Anti-PD-1 (Nivolumab biosimilar - IgG1fut isotype)

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Anti-hPD1-Ni-hIgG1fut

Human PD-1 (Nivolumab) antibody - Human IgG1, non-fucosylated

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3 x 100 µg

hpd1ni-mab13-3
+-
$298
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Non-fucosylated human IgG1 monoclonal antibody (mAb) against human PD-1

Principle of PD-1/PD-L1 cellular assay
Principle of PD-1/PD-L1 cellular assay
(click to enlarge)

Anti-hPD1-Ni-hIgG1fut features the constant region of the human IgG1 isotype and the variable region of nivolumab. Nivolumab is a fully human IgG4 (S228P) monoclonal antibody that targets the programmed cell death 1 (PD-1) receptor found on activated T cells, B cells, and myeloid cells. Under normal physiological conditions, PD-1 negatively regulates T cell activation thereby preventing autoimmunity [1]. Under pathological conditions, cancer cells produce PD-L1 (programmed cell death 1 ligand 1), the agonist that binds and activates PD-1. Activated PD-1 enables the cancer cells to evade the immune system. Nivolumab binds and blocks the activation of the PD-1 receptor, thereby resulting in the activation of T cells and cell-mediated immune responses [2, 3]. This antibody contains an engineered hinge region mutation (S228P) designed to prevent exchange of IgG4 molecules. Nivolumab has been approved by the FDA for the treatment of melanoma and metastatic squamous non-small cell lung cancer (NSCLC). 

Anti-hPD1-Ni-hIgG1fut is a non-fucosylated antibody. The absence of the fucose residue from the N-glycans of IgG-Fc results in dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC) without any detectable change in complement-dependent cytotoxicity (CDC) or antigen binding capability [4, 5]. It has been produced in Chinese hamster ovary (CHO) cells that are deficient for fucosylation and purified by affinity chromatography with protein G.

 

References:

1. McDermott D. & Atkins M., 2013. PD-1 as a potential target in cancer therapy. Cancer Med. 2: 662–73.
2. Wang C. et al., 2014. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS- 936558, and in vivo toxicology in non-human primates..Cancer Immunol Res. 2:846-56.
3. Gunturi A. & McDermott DF., 2015. Nivolumab for the treatment of cancer. Expert Opin Investig Drugs. 24:253-60.
4. Yamane-Ohnuki N. & Satoh M., 2009. Production of therapeutic antibodies with controlled fucosylation.corresponding MAbs. 1(3): 230–236.
5. Mizushima T., 2011. Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans. Genes Cells. 16(11): 1071–1080

Figures

ADCC assay using various anti-human PD-1 (Nivolumab) antibody isotypes and Raji-hPD-1 target cells
ADCC assay using various anti-human PD-1 (Nivolumab) antibody isotypes and Raji-hPD-1 target cells

Comparison of ADCC potency for native and engineered anti-human PD-1 antibody isotypes: Raji-hPD-1 cells were incubated with gradient concentrations of Anti-hPD-1 or Anti-β-galactosidase (β-gal) mAbs for 1 hour. Jurkat-Lucia™ NFAT-CD16 effector cells were then co-incubated with targets cells for 6 hours. NFAT activation, reflecting the induced ADCC response,  was assessed by determining Lucia luciferase activity in the supernatant using QUANTI-Luc™. Percentages of the maximal response normalized to the IgG1 isotype are shown.

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Specifications

Specificity: Targets cells expressing human PD-1

Clonality: Monoclonal antibody

Isotype: Human IgG1, kappa

Source: CHO cells

Formulation: 0.2 μm filtered solution in a sodium phosphate buffer with glycine, saccharose and stabilizing agents

Purity: Purified by affinity chromatography with protein G

Quality control:

  • Binding to human PD-1 has been tested using flow cytometry.
  • The complete sequence of this antibody has been verified.
  • The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.
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Contents

  • 3 x 100 µg Anti-hPD1-Ni-hIgG1fut provided azide-free and lyophilized

room temperature Product is shipped at room temperature.

store Upon receipt, store at -20°C.

 

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