Atezolizumab

Catalog No.A2004 Synonyms: MPDL3280A

For research use only. Not for use in humans.

Atezolizumab is a fully humanized, IgG1 monoclonal antibody that blocks the interaction of PD-L1 with both PD-1 and B7.1, but not the interaction of PD-L2 with PD-1. MW : 145 KD.

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Choose Selective PD-1/PD-L1 Inhibitors

Biological Activity

Description Atezolizumab is a fully humanized, IgG1 monoclonal antibody that blocks the interaction of PD-L1 with both PD-1 and B7.1, but not the interaction of PD-L2 with PD-1. MW : 145 KD.
Targets
hPD-L1 [2]
(Cell-free assay)
0.4 nM(Kd)
In vitro

A key feature of atezolizumab is that it is FcγR-binding deficient, so it cannot bind to Fc receptors on phagocytes and therefore does not cause antibody-dependent cell-mediated cytotoxicity (ADCC). atezolizumab treatment could bring cytokine changes include transient increases in IL-18, IFNγ, and CXCL11, and a transient decrease in IL-6; cellular changes include increases in proliferating CD8+ T cells[1].

In vivo By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironement and consequently increases T cell mediated immunity against the tumor. The pharmacokinetics of atezolizumab were initially studied in cynomolgus monkeys and mice where its volume of distribution was calculated to be approximately that of the plasma volume. The in vivo biodistribution of atezolizumab 24 hours after infusion is, in order of magnitude, the spleen, lungs, kidneys, liver, heart, and muscle. In tumor bearing animals, the drug also accumulates intratumorally, initially at the pushing border of the tumor and progressing later to the tumor core, particularly if the tumor is necrotic. The pharmacokinetic curve of atezolizumab is dose-dependent (non-linear) because of target mediated drug disposition (binding of drug to the PD-L1 ligand in the body). Saturation of PD-L1 receptors by atezolizumab on circulating CD4 and CD8 T cells occurs between 24 and 48 hours after dosing with serum concentrations > 0.5 μg/mL[1]. MPDL3280A binds to PD-L1 in monkey and human with comparable affinity between species[2].

Protocol

Cell Research:

[3]

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  • Cell lines: DCCIKs lymphocytes
  • Concentrations: 5 μg/mL
  • Incubation Time: 24 h
  • Method:

    The in vitro cytotoxicity of the DCCIKs used as effector cells in the absence or presence of 5 μg/mL MPDL3280A against CaSki cells employed as target cells at a ratio of 10:1, 30:1 and 90:1 was determined using a CCK8 kit. The effector and target cells were added to 96-well plates and incubated for 24 h. The groups comprising a mixture of cell types were the experimental groups, whereas the control groups contained only one cell type of the CaSki cells, DCCIKs or 1640 RPMI cultivating solution. The CCK8 assay was performed in triplicate and optical density (OD) was read at 570 nm[3].

     

    Objective: Antibody-dependent cellular cytotoxicity Cells: UDHL cells, 293 cells and human PBLs Concentrations: Incubation Time: Method: In an in vitro assay for antibody dependent cellular cytotoxicity (using human PBLs as effectors), the engineered antibody was unable to mediate the killing of two cell lines transfected with human PD-L1, while efficient killing was observed using the unmodified ‘wild-type’ antibody[4].

     

    Atezolizumab can apply to humanized mice, non-humanized mice, peripheral blood and other related assays


    (Only for Reference)
Animal Research:

[2]

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  • Animal Models: Cynomolgus monkeys
  • Formulation: 20 mM his-acetate, 0.02% polysorbate 20, 240 mM sucrose, pH 5.5
  • Dosages: 0.5, 5 and 20 mg/kg
  • Administration: i.v.
    (Only for Reference)

Product Details

Formulation PBS buffer, pH 7.2
Isotype Human IgG
Source CHO cells
Storage Store at -80°C and avoid freeze-thaw cycles.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID