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Atezolizumab

Cat. No. M6101
Atezolizumab Structure
Synonym:

MPDL3280A,Anti-PD-L1;Tecentriq

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5mg USD 600  USD600 In stock
10mg USD 1000  USD1000 In stock
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Quality Control & Documentation
Biological Activity

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.

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. MPDL3280A binds to PD-L1 in monkey and human with comparable affinity between species.

In contrast, atezolizumab was able to interact with the mPD-L1, block the mPD-L1/hPD-L1 immune checkpoint in a cell-based assay, and provide inhibition of the growth of mouse tumors in a syngeneic mouse model, where the mPD-L1/mPD-1 immune checkpoint is present.

Product Citations
Protocol (for reference only)
Cell Experiment
Cell lines DCCIKs lymphocytes
Preparation 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.
Concentrations 5 μg/mL
Incubation time 24 h
Animal Experiment
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.
Chemical Information
CAS Number 1380723-44-3
Form Liquid
Storage Store at -20°C or -70°C. Avoid multiple freeze-thaws.
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Junshang Ge, et al. Cancer Res. Epstein-Barr virus-encoded circular RNA circBART2.2 promotes immune escape of nasopharyngeal carcinoma by regulating PD-L1

[2] Katarzyna Magiera-Mularz, et al. iScience. Human and mouse PD-L1: similar molecular structure, but different druggability profiles

[3] Huang A, et al. Sci Rep. A human programmed death-ligand 1-expressing mouse tumor model for evaluating the therapeutic efficacy of anti-human PD-L1 antibodies.

[4] Lesniak WG, et al. Bioconjug Chem. PD-L1 Detection in Tumors Using [(64)Cu]Atezolizumab with PET.

[5] Fehrenbacher L, et al. Lancet. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.

[6] Chatterjee S, et al. Oncotarget. A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors.

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Keywords: Atezolizumab, MPDL3280A,Anti-PD-L1;Tecentriq supplier, PD-1/PD-L1, inhibitors, activators


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