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B-hPD-1/hPD-L1 mice
Strain Name C57BL/6-Pdcd1tm1(PDCD1)Cd274tm1(CD274)/Bcgen Common Name  B-hPD-1/hPD-L1 mice
Background C57BL/6 Catalog number  120522
Aliases 
PDCD1 (Programmed death-1,as known as PD-1) ;
CD274
(Programmed cell death ligand-1,also known as B7-H1, PD-L1)

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. PD-L1 (Programmed cell death ligand-1), also known as B7-H1 and CD274, is mainly expressed in antigen-presenting cells (APCs) and activated T cells, and is one of the two ligands of PD-1. The interaction between PD1 and PD-L1 plays an important role in the negative regulation of the immune response. PD-L1 is highly expressed in a variety of solid tumors. PD-1 and PD-L1 interactions can reduce T Cell Activation and promote tumor immune escape. The PD-1/PD-L1 signaling pathway can be blocked and antitumor immune response can be restored by using by anti-PD-1 or anti-PD-L1 antibodies to block the binding of PD1 to PD-L1.


Protein expression analysis




Strain specific PD1 and PD-L1 expression analysis in homozygous B-hPD-1/hPD-L1 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1 (H/H) mice stimulated with anti-CD3ε in vivo , and analyzed by flow cytometry with species-specific anti-PD-1 and anti-PD-L1 antibodies. Mouse PD-1 and PD-L1 were exclusively detectable in WT mice. Human PD-1 and PD-L1 were exclusively detectable in homozygous B-hPD-1/hPD-L1 mice but not in WT mice.


In vivo efficacy of anti-human PD-1 antibody



Antitumor activity of anti-human PD-1 antibody in B-hPD-1/hPD-L1 mice. (A) Anti-human PD-L1 antibody Pembrolizumab (in house) inhibited MC38-hPD-L1 tumor growth in B-hPD-1/hPD-L1 mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1/hPD-L1 mice (male, 8-week-old, n=5). Mice were grouped when tumor volume reached approximately 80mm3, at which time they were treated with anti-human PD-1 antibody with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, different doses of human PD-1 antibody inhibited tumor growth in different levels, demonstrating that the B-hPD-1/hPD-L1 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



Antitumor activity of anti-human PD-L1 antibody in B-hPD-1/hPD-L1 mice. (A) Anti-human PD-L1 antibody atezolizumab (in house) inhibited MC38-hPD-L1 tumor growth in B-hPD-1/hPD-L1 mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1/hPD-L1 mice (male, 8-week-old, n=5). Mice were grouped when tumor volume reached approximately 80mm3, at which time they were treated with anti-human PD-L1 antibody with doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, different doses of human PD-L1 antibody inhibited tumor growth in different levels, demonstrating that the B-hPD-1/hPD-L1 mice provide a powerful preclinical model for in vivo evaluation of anti-human PD-L1 antibodies. Values are expressed as mean ± SEM.