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Animal Models and Cell Lines

>Double Humanized Immune-Checkpoint Mice

Strain description

 

Strain Name 

C57BL/6-Pdcd1tm1(hPDCD1)Ctla4tm1(hCTLA4)/Bcgen  

Common Name

B-hPD-1/hCTLA4 mice

Background  

C57BL/6

Catalog number 

B-DM-004

Catalog number (Males) 

BDM004M 

Catalog number (Females) 

BDM004F

Related Genes

 

PD-1(Programmed death-1) ;

CTLA4 (Cytotoxic T-lymphocyte-associated protein 4,CD152)

 

mRNA expression analysis

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Fig 1. RT-PCR analysis of the B-hPD-1/hCTLA4 humanized mice.

The splenocytes of the B-hPD-1/hCTLA4 homozygous mice showed expression of human PD-1 and CTLA4 mRNA but not mouse PD-1 and CTLA4 mRNA.

 

Protein expression analysis

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Fig 2. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1 /hCTLA4 mice were analyzed by flow cytometry.

Mouse CTLA4+ T cells were detected in the WT mice, while human CTLA4+ T cells were detected in the homozygous B-hPD-1 /hCTLA4 mice.

 1535532540516209.png

Fig 3. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1 /hCTLA4 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 homozygous B-hPD-1 /hCTLA4 mice.

  

Combination therapy of PD-1(Keytruda) Ab and CTLA4(Yervoy) Ab

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Fig 4. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hCTLA4 mice. Mice were grouped when the tumor size was approximately 150±50 mm3 (n=5). Anti-hCTLA4 antibody Yervoy and the anti-hPD-1 antibody Keytruda show modest inhibition of tumor growth. On the other hand, combination of anti-hCTLA4 antibody Yervoy and the anti-hPD-1 antibody Keytruda shows almost complete inhibition when compared to single Ab treatment. B-hPD-1/hCTLA4 mouse model is a powerful tool for in vivo evaluation of combination therapy efficacy for hPD-1 antibodies and hCTLA4 antibodies . (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

 

 

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