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B-hPD-1 mice

2017-05-09 17:42:09.0

Strain Description


Strain NameC57BL/6-Pdcd1tm1(hPDCD1)/BcgenCommon NameB-hPD-1 mice

Background

C57BL/6Catalog numberB-CM-001

Catalog number 

(Males)

BCM001M

Catalog number

(Females)

BCM001F
Related GenesPd-1 (Programmed death-1)


Gene Description:

PD-1 (Programmed death-1) is mainly expressed on the surface of T cells and primary B cells. The two PD-1 ligands, PD-L1 and PD-L2, are widely expressed on antigen-presenting cells (APCs). PD-1 interacts with its ligands and plays an important role in the negative regulation of the immune response. PD-L1 protein expression is detected in many human tumor tissues. PD-L1 expression in tumor cells could be induced by the microenvironment of tumor cells. PD-L1 expression is favorable for tumorigenesis and growth, for induction of anti-tumor T Cell apoptosis, and for escaping responses by the immune system. 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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mRNA Expression Analysis

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Fig 1. RT-PCR Analysis of B-hPD-1 Mice The hPD-1 mRNA, but not mPD-1 mRNA was detected in splenocytes of the homozygous B-hPD-1 mice.




Protein Expression Analysis

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Fig 2. FACS Analysis of B-hPD-1 Mice

Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1 mice were analyzed by flow cytometry.

Mouse PD-1+ T cells were detected in the WT C57BL/6 mice, while human PD-1+ T cells were detected in the homozygous B-hPD-1 mice.









Model verification


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Fig 3. Anti-hPD-1 Ab treated in B-hPD-1 mice and C57BL/6 mice.

Murine colon tumor MC38 cells were subcutaneously implanted into homozygous B-hPD-1 mice (A) and wild type C57BL/6 mice (B). Mice were grouped when the tumor size was approximately 100 mm3. Human PD-1 antibody X2 significantly inhibited tumor growth in the homozygous B-hPD-1 mice but not in the wild type C57BL/6 mice, suggesting that B-hPD-1 mouse model is a powerful tool for in vivo PD-1 antibody pharmacological efficacy studies.


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Fig 4. B-hPD-1 mice and C57BL/6 mice treated with anti-hPD-L1 Ab (Tecentriq).

Murinecolon tumor MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1 mice (A) and wild type C57BL/6 mice (B). Mice were grouped when the tumor size was approximately 100 mm3. Anti-hPD-L1 Ab (Tecentriq) significantly inhibited tumor growth in the both homozygous B-hPD-1 mice and wild type C57BL/6 mice.


PD-1(Keytruda) Ab Efficacy Evaluation (MC38 Cell line)

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Fig 5. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1 mice. 

Mice were grouped when the tumor size was 150±50 mm3 (n=5). The high dose, mid dose and low dose of human PD-1 antibody Keytruda all significantly inhibited tumor growth, confirming that the B-hPD-1(v1) mouse model is a powerful tool for in vivo PD-1 antibody pharmacological efficacy studies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.


PD-1(Keytruda) Ab Efficacy Evaluation (EL-4 Cell line)

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Fig 6. Murine lymphoma EL-4 cells were subcutaneously implanted into homozygous B-hPD-1 mice. 

Mice were grouped when the tumor size was 150±50 mm3 (n=5). Different doses of human PD-1 antibody Keytruda all obviously inhibited tumor growth, confirming that the B-hPD-1(v1) mouse model is a powerful tool for in vivo PD-1 antibody pharmacological efficacy studies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.


PD-L1(Tecentriq) Ab Efficacy Evaluation

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Fig 7. Murine colon cancer MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1 mice. Mice were grouped when the tumor size was approximately 100 mm3 (n=7). The human PD-L1 antibody Tecentriq significantly inhibited tumor growth, confirming that the B-hPD-1(v1) mouse model is a powerful tool for in vivo PD-L1 antibody pharmacological efficacy studies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.


Combination therapy of PD-1(Keytruda) Ab/PD-L1(Tecentriq)Ab and chemotherapy drugs


Combination Therapy of PD-1(Keytruda) Ab and Chemotherapy Drugs

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Fig 8. Murine colon cancer MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1 mice. 

Mice were grouped when the tumor size was approximately 150±50 mm3 (n=8). ). The combination of anti-hPD-1 antibody Keytruda and the chemotherapy drug Cisplatin shows more inhibitory effects than individual groups, suggesting that B-hPD-1 mouse is a powerful tool for in vivo evaluating combination therapy efficacy in vivo. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.


Combination Therapy of PD-L1(Tecentriq) Ab and Chemotherapy Drugs

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Fig 9. Murine colon cancer MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1 mice. Mice were grouped when the tumor size was approximately 100 mm3 (n=7). ). The combination of anti-hPD-L1 antibody Tecentriq and the chemotherapy drug Cisplatin shows more inhibitory effects than individual groups, suggesting that B-hPD-1(v1) mouse is a powerful tool for evaluating combination therapies in vivo. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

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