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PD-1/PD-L1 Antibody Pharmacological Models

2017-05-25 16:07:41.0

Tumor immunotherapy is one of the promising research directions for tumor treatments. Science magazine has ranked tumor immunotherapy first among the ten scientific breakthroughs in 2013. At present, research for a PD-1/PD-L1 pathway inhibitor has been widely focused on.

The B-hPD-1 humanized mouse model developed by Biocytogen can be used for research on PD-1/PD-L1 signaling mechanisms, for toxicology research, and for screening the development of PD-1/PD-L1 antibodies. This model provides an effective tool for drug screening in vivo, largely accelerates the development process of antibody-based drugs, reduces the time and cost of preclinical tests, and reduces the risk during drug development.


B-hPD-1 mouse: powerful model for R & D of PD-1 and PD-L1 inhibitor


C57BL/6 genetic background:

This inbred mouse line is commonly used for oncology, physiology, immunology and genetics research. Using these mice will yield experimental results of high precision, good comparability, and stress response uniformity, so that your efficacy test results are more uniform and reliable.

Pd-1 genetic humanization:

Partial sequence including the Igv is humanized, and the main combination position of the PD-1 inhibitor of PD-1 antibody is well conserved.


PD-1/PD-L1 antibody pharmacological verification

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Fig 1. Murine colon tumor MC38 cells were subcutaneously implanted into homozygous B-hPD-1 mice. Mice were grouped when the tumor sizes were about 100mm3 (n=4). The human PD-1 antibodyKeytruda significantly inhibited tumor growth, verifying that the B-hPD-1 mouse model is a powerful tool for in vivo pharmacological efficacy tests. (A) Tumor average volume ±SEM; (B) Mice average weight ±SEM.

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Fig 2. Murine colon tumor MC38 cells (murine Pd-L1 gene is inhibited, human PD-L1 gene is overexpressed) were subcutaneously implanted  into homozygous B-hPD-1 mice. Mice were grouped when the tumor sizes were about 100mm3 (n=7). The anti-human PD-L1 antibodysignificantly inhibited tumor growth, verifying that B-hPD-1 mice are powerful tools for PD-L1 antibody in vivo pharmacological efficacy tests. (A) Tumor average volume ±SEM; (B) Mice average weight ±SEM.


Combination therapy of PD-L1 antibodies and chemotherapy drugs:

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Fig 3. Subcutaneous tumor model was established by transplanting modified mouse colon cancer MC38 cells (replace mPD-L1 with hPD-L1) into B-hPD-1 homozygous mice. Animals were grouped (n=7) when the tumor size is approximately 100 mm3. Combination of anti-hPD-L1 antibody Atezolizumab and chemotherapy drug Cisplatin shows more inhibitory effects than individual groups, suggesting B-hPD-L1 mouse is a powerful tool for evaluating in vivo combination therapy efficacy of hPD-L1 antibodies and chemotherapy drugs. A. The mean size of tumor, average±SEM, B. Mouse body weigh, average±SEM.



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