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Animal Models and Cell Lines

>Double Humanized Immune-Checkpoint Mice

Strain description

 

Strain Name

C57BL/6-Pdcd1tm1(hPDCD1)Tnfrsf4tm1(hTNFRSF4)/Bcgen

Common Name

B-hPD-1/hOX40 mice

Background

C57BL/6

Catalog number

B-DM-006

Catalog number (Males)

BDM006M

Catalog number (Females)

BDM006F

Related Genes

PD-1(Programmed death-1) ;

Tnfrsf4(Tumor necrosis factor receptor superfamily, member 4, also known as OX40)

 

mRNA expression analysis

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Fig 1. RT-PCR analysis of the B-hPD-1/hOX40 humanized mice.

The splenocytes of the B-hPD-1/hOX40 homozygous mice showed expression of human PD-1 and OX40 mRNA but not mouse PD-1 and OX40 mRNA.


Protein expression analysis

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Fig 2. Splenocytes from both wild type (WT)  C57BL/6  and homozygous B-hPD-1/hOX40 mice were analyzed  by flow cytometry. 

Mouse OX40+ T cells were detected in the WT C57BL/6  mice, while human OX40+ T cells were detected in the  homozygous B-hPD-1/hOX40 mice.


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Fig 3. Splenocytes from both wild t ype (WT) C57BL/6 and homozygous B-hPD-1/hOX40 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/hOX40 mice.


Combination therapy of PD-1(Keytruda) Ab and OX40 Ab

 

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Fig 4. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hOX40 mice.

Mice were grouped when the tumor size was approximately 150±50 mm3 (n=6). Anti-hOX40 antibody and the anti-hPD-1 antibody Keytruda show inhibitory effects on tumor growth. On the other hand, combination of anti-hOX40 antibody and the anti-hPD-1 antibody Keytruda shows almost complete inhibition when compared to single Ab treatment. B-hPD-1/hOX40 mouse model is a powerful tool for is a powerful tool for in vivo efficacy evaluation of hPD-1 and hOX40 antibodies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.


Combination therapy of PD-1(Keytruda) Ab and OX40 Ab

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Fig 5. Murine melanoma B16-F10-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1/hOX40 mice.

Mice were grouped when the tumor size was approximately 150±50 mm3 (n=5). Combination of anti-hOX40 antibody and the anti-hPD-1 antibody Keytruda shows higher inhibitory effects than single antibody treatment. B-hPD-1/hOX40 mouse model is a powerful tool for is a powerful tool for in vivo efficacy evaluation of hPD-1 and hOX40 antibodies combination therapy. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.


 

 

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