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Animal Models and Cell Lines

>Double Humanized Immune-Checkpoint Mice

Strain Description

 

Strain NameC57BL/6-Pdcd1tm1(hPDCD1)Cd137tm1(hCD137)/BcgenCommon NameB-hPD-1/h4-1BB mice
BackgroundC57BL/6Catalog numberB-DM-001
Catalog number (Males)BDM001MCatalog number (Females)BDM001F
Related Genes

PD-1(Programmed death-1) ;

TNFRSF9(TNF receptor superfamily member 9, also known as 4-1BB


mRNA expression analysis

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Fig 1. RT-PCR analysis of the B-hPD-1/h4-1BB humanized mice.

The splenocytes of the B-hPD-1/h4-1BB homozygous mice showed expression of human PD-1 and 4-1BB mRNA but not mouse PD-1 and 4-1BB mRNA.


 

Protein expression analysis 

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Fig 2.Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/h4-1BB mice were analyzed by flow cytometry.

Mouse 4-1BB+ T cells were detected in the WT C57BL/6 mice, while human 4-1BB+ T cells were detected in the homozygous B-hPD-1/h4-1BB mice.


 

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Fig 3.Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/h4-1BB 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/h4-1BB mice.

 

Combination therapy of PD-1 (Keytruda) mAb and 4-1BB antibody (Urelumab Analog) (MC38 cell line)

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Fig 4.  Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1/h4-1BB mice.

Mice were divided into control and treatment grouped (n=5) when the tumor size was approximately 150 ± 50mm3 (n=6). Anti-hPD-1 antibody and anti-h4-1BB antibody significantly inhibited tumor growth in the homozygous B-hPD-1/h4-1BB mice, suggesting that B-hPD-1/h4-1BB mouse model is an effective tool for in vivo efficacy evaluation of hPD-1 and h4-1BB antibody combination therapy. Theaverage±SEM of tumor sizes are shown in the figure.


 

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