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

Protein Expression Analysis

Strain specific PD-1 expression analysis in homozygous B-hPD-1 mice by flow cytometry.

Splenocytes were collected from WT and homozygous B-hPD-1 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-PD-1 antibody. Mouse PD-1 was detected in WT mice. Human PD-1 was exclusively detected in homozygous B-hPD-1 mice but not WT mice.

Application

In vivo efficacy of anti-human PD-1 antibody

Antitumor activity of anti-human PD-1 antibody in B-hPD-1 mice and C57BL/6 mice.

Anti-human PD-1 antibody inhibited MC38 tumor growth in B-hPD-1 mice. (A) Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 6 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-1 antibody and schedules indicated in panel A, as shown in panel A, human PD-1 antibody X2 efficacious in controlling tumor growth in the homozygous B-hPD-1 mice but not in the wild type C57BL/6 mice (B) The results demonstrating that B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.

Antitumor activity of anti-human PD-L1 antibody in B-hPD-L1 and C57BL/6 mice.

Anti-human PD-L1 antibody atezolizumab inhibited MC38-hPD-L1 tumor growth in B-hPD-L1 mice (A) and wild type C57BL/6 mice (B). Murine colon cancer MC38-hPD-L1 cells (2×105) were subcutaneously implanted into homozygous B-hPD-1 mice and C57BL/6 (female, 6-8 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-L1 antibody with doses and schedules indicated in panel , human PD-L1 efficacious in controlling tumor growth in homozygous B-hPD-1 mice and wild type C57BL/6 mice (B). Values are expressed as mean ± SEM.

Antitumor activity of anti-human PD-1 antibody (pembrolizumab) in B-hPD-1 mice.

(A) Pembrolizumab inhibited MC38 tumor growth in B-hPD-1 mice. Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 6 week-old, n=10). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-1 antibody with doses and schedules indicated in panel A. (B) Body weight changes during treatment. As shown in panel A, anti-human PD-1 antibody was efficacious in controlling tumor growth in B-hPD-1 mice, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.

Antitumor activity of anti-human PD-1 antibody in B-hPD-1 mice.

(A) Anti-human PD-1 antibody inhibited MC38 tumor growth in B-hPD-1 mice. Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 4-6 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with three anti-human PD-1 antibodies with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, anti-human PD-1 antibodies were efficacious in controlling tumor growth in B-hPD-1 mice, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.

Antitumor activity of anti-human PD-1 antibody in B-hPD-1 mice.

(A) Anti-human PD-1 antibody inhibited MC38 tumor growth in B-hPD-1 mice. Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (male, 4-6 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human PD-1 antibody with doses and schedules indicated in panel (A). (B) Body weight changes during treatment. As shown in panel A, anti-human PD-1 antibody was efficacious in controlling tumor growth in B-hPD-1 mice, demonstrating that B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.

Antitumor activity of anti-human PD-1 antibody in B-hPD-1 mice.

(A) Anti-human PD-1 antibody inhibited EL4 tumor growth in B-hPD-1 mice. Murine lymphoma cancer EL4 cells were subcutaneously implanted into homozygous B-hPD-1 mice (n=5). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with three anti-human PD-1 antibodies with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, anti-human PD-1 antibodies were efficacious in controlling tumor growth in B-hPD-1 mice, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-1 antibodies. Values are expressed as mean ± SEM.

In vivo efficacy of anti human PD-L1 antibody

Combination therapy of anti-human PD-1 Ab and chemotherapy drug

Antitumor activity of anti-human PD-1 antibody combined with cisplatin in B-hPD-1 mice.

(A) Anti-human PD-1 antibody combined with cisplatin inhibited MC38-hPD-L1 tumor growth in B-hPD-1 mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 5-8 week-old, n=8). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with anti-human PD-1 antibodies and cisplatin with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, combination of anti-hPD-1 antibody and the chemotherapy drug cisplatin shows more efficaciously inhibitory effects than individual groups, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of hPD-1 antibodies and chemotherapy drugs. Values are expressed as mean ± SEM.

Combination therapy of anti-human PD-1 Ab and chemotherapy drug

Antitumor activity of anti-human PD-L1 antibody combined with cisplatin in B-hPD-1 mice.

(A) Anti-human PD-L1 antibody combined with cisplatin inhibited MC38-hPD-L1 tumor growth in B-hPD-1 mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1 mice (female, 5-8 week-old, n=8). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with anti-human PD-L1 antibody and cisplatin with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, combination of anti-hPD-L1 antibody and the chemotherapy drug cisplatin shows more efficaciously inhibitory effects than individual groups, demonstrating that the B-hPD-1 mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of hPD-L1 antibodies and chemotherapy drugs. Values are expressed as mean ± 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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