Basic Information

Strain Name
C57BL/6-Pdcd1tm1(PDCD1)Bcgen/Bcgen
Stock Number
110003
Common Name
B-hPD-1 mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
Pd-1 (Programmed death-1)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous

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 tumor escape from immune system 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

Details

Phenotype

mRNA Expression Analysis

mRNA-B-hPD

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

Protein Expression Analysis

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

Application

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

B-hPD-1-Anti-hPD-1

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 study.

Anti-hPD-L1 Ab (Tecentriq) treated in B-hPD-1 mice and C57BL/6 mice

B-hPD-1-Tecentriq

Murine colon 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) Efficacy Evaluation

B-hPD-1-Keytruda

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=10). The human PD-1 antibody Keytruda significantly inhibited tumor growth, confirming that the B-hPD-1 mouse model is a powerful tool for in vivo PD-1 antibody pharmacological efficacy study. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

PD-1 (Keytruda) Efficacy Evaluation (Different Doses)

B-hPD-1-Keytruda-Different-1

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 mouse model is a powerful tool for in vivo PD-1 antibody pharmacological efficacy study. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

PD-1 (Keytruda) Efficacy Evaluation (Different Doses)

B-hPD-1-Keytruda-Different-2

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). Different doses of human PD-1 antibody Keytruda inhibited tumor growth on different levels, confirming that the B-hPD-1 mouse model is a powerful tool for in vivo PD-1 antibody pharmacological efficacy study. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

PD-1 (Keytruda) Efficacy Evaluation (EL-4 Cells Tumor Model)

B-hPD-1-EL-4

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 mouse model is a powerful tool for in vivo PD-1 antibody pharmacological efficacy study. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

PD-L1 (Tecentriq) Efficacy Evaluation

B-hPD-1-Effic

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 mouse model is a powerful tool for in vivo PD-L1 antibody pharmacological efficacy study. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

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

B-hPD-1-Chemo

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)). 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 of hPD-1 antibodies and chemotherapy drugs. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

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

B-hPD-1-PD-L1

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). Combination of anti-hPD-L1 antibody Tecentriq 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 of hPD-1 antibodies and chemotherapy drugs. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

References

  1. Nat Commun.2017 Feb 6;8:14369. doi: 10.1038/ncomms14369.
  2. EMBO J.1992 Nov;11(11):3887-95.
  3. J Exp Med.2000 Oct 2;192(7):1027-34.
  4. 2001 Jan 12;291(5502):319-22.
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