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B-hPD-1 mice (PD-1 humanized mice)

2017-05-09 17:42:09.0

Basic characteristics:


PD-1 (programmed death-1) is mainly expressed on the surface of T cells and primary B cells. PD-1 ligands, PD-L1 and PD-L2, are widely expressed on antigen-presenting cells (APCs). PD-L1 and PD-L2 interact with their receptor and plays a significant role in the negative regulation of the immune response. Inhibition of PD-1 binding to its ligand can result in tumor cells that are exposed to the killing version of the immune system, and thus is a target for cancer treatments.


Targeting strategy:


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Flow cytometry verification:

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Fig 1. Spleen cells from both wild type (WT) C57BL/6 and B-hPD-1 homozygous mice were analyzed by flow cytometry. Mouse PD-1+ T cells were detected in the WT mice, while human PD-1+ T cells were detected in the B-hPD-1 homozygous mice.



Model verification:

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Fig 2. Murine colon tumor MC38 cells were subcutaneously implanted into homozygous B-hPD-1 mice (A) and C57BL/6 mice (B). MC38 tumors in B-hPD-1 or C57 mice were treated by human PD-1 antibody X2. MC38 tumors responded to PD-1 antibody treatment in humanized B-hPD-1 mice but not in C57 mice, indicating the necessity of PD-1 humanization for in vivo efficacy test.

PD-1/PD-L1 antibody pharmacological verification:

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Fig 3. Murine colon tumor MC38 cells were subcutaneously injected into the B-hPD-1 homozygous mice, which were grouped when the tumor size reached 100 mm3 (n=4). The human PD-1 antibody Keytruda significantly inhibited tumor growth (A), but not body weight (B), verifying that the B-hPD-1 mouse model is a powerful tool for human PD-1 antibody in vivo pharmacological efficacy tests.


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Fig 4. Modified murine colon tumor MC38 cells with mPD-L1 replaced by hPD-L1 were subcutaneously injected into the B-hPD-1 homozygous mice, which were grouped when the tumor size reached 100 mm3 (n=7). The human PD-L1 antibody Atezolizumab significantly inhibited tumor growth (A), but not body weight (B), verifying that the B-hPD-1 mice are powerful tools for human PD-L1 antibody in vivo pharmacological analysis and verification.


Combination therapy of PD-L1 antibodies and chemotherapy drugs:

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Fig 5. Modified murine colon tumor MC38 cells with mPD-L1 replaced by hPD-L1 were subcutaneously injected into the B-hPD-1 homozygous mice, which were grouped when the tumor size reached 100 mm3 (n=7). Combination of the human PD-L1 antibody Atezolizumab and the chemotherapy drug Cisplatin shows a significantly larger inhibitory effect on tumor growth than individual treatment (A), but not body weight (B), suggesting that the B-hPD-1 mouse model is a powerful tool for evaluating in vivo combination therapy efficacy of human PD-L1 antibodies and chemotherapy drugs in vivo pharmacological efficacy tests.

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