Atezolizumab

製品コードA2004 別名: MPDL3280A Non-humanized mouse model applicable

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.

サイズ 価格(税別)  
JPY 117362.00

質量管理及び製品安全説明書

PD-1/PD-L1阻害剤の選択性比較

生物活性

製品説明 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.
ターゲット
hPD-L1 [2]
(Cell-free assay)
0.4 nM(Kd)
体外試験

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].

体内試験 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].

お薦めの試験操作(参考用のみ)

細胞試験:
+ 展開
  • Objective: Antibody-dependent cellular cytotoxicity (ADCC)
    Cells: UDHL cells(lymphoma cell line), 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.
    Reference: https://www.ncbi.nlm.nih.gov/pubmed/25428504

    Objective: Determine the binding of [111In]PD-L1-mAb to tumor cell lines
    Cells: NCI-H2444(Lung Cancer cell line), MDAMB231(Breast Cancer cell line),etc
    Concentrations: 1 μCi/100μl
    Incubation Time: 1 h
    Method: Incubating 1 μCi of [111In]PD-L1-mAb with 1×106cells (in triplicate for each cell line) for 1h at 37°C. PD-L1 blocking was performed by adding a 10-fold molar equivalent excess of the non-labeled mAb. After incubation, cells were washed three times with cold PBS prior to counting on an automated gamma counter.
    Reference: https://www.ncbi.nlm.nih.gov/pubmed/26848870

    Atezolizumab can apply to humanized mice, non-humanized mice (eg: C57BL/6 mice), peripheral blood and other related assays (Only for Reference)
動物試験:
+ 展開
  • Objective: To determine the effect of anti-hPD-L1 antibody on human PD-L1-expressing mouse tumor model
    Animal Models: Female C57BL/6 mice were subcutaneous inoculated with MC-38-hPD-L1 cells
    Formulation: PBS
    Dosages: 1 mg/kg, 3 mg/kg, 10 mg/kg
    Administration: i.p.
    Reference: https://www.ncbi.nlm.nih.gov/pubmed/?term=28202921

    Objective: Developed and evaluated radiolabeled [111In] PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb (Atezolizumab) for non-invasive imaging of PD-L1 expression in tumors
    Animal Models: NSG mice (humanized mice) were implanted subcutaneously with CHO-PDL1, CHO, H2444 H1155 cells and orthotopically in the upper mammary fat pads with MDAMB231 and SUM149 cells
    Formulation: 14.8 MBq (400 μCi) of [111In]PD-L1-mAb or 22 μg of NIR-PD-L1-mAb
    Dosages: 200 μg per injection
    Administration: i.v.
    Reference: https://www.ncbi.nlm.nih.gov/pubmed/26848870

    Atezolizumab can apply to humanized mice, non-humanized mice (eg: C57BL/6 mice), peripheral blood and other related assays (Only for Reference)

製品説明

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