Basic Information

Strain Name
C57BL/6-Pdcd1tm1(PDCD1)Tnfrsf4tm1(TNFRSF4)/Bcgen
Stock Number
120521
Common Name
B-hPD-1/hOX40 mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
PD-1 (Programmed death-1); Tnfrsf4 (Tumor necrosis factor receptor superfamily, member 4, also known as OX40)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous
NCBI Gene ID

Targeting Strategy

Details

Phenotype

mRNA Expression Analysis

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

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

 

Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hOX40 mice were analyzed by flow cytometry. Mouse PD-1+ T cells were detectable in the WT C57BL/6 mice, while human PD-1+ T cells were detectable in the homozygous B-hPD-1/hOX40 mice.

Application

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

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

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.

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. Science. 2001 Jan 12;291(5502):319-22.
  5. J Immunol. 2013 Oct 1;191(7):3641-50.
  6. Cancer Res. 2013 Dec 15;73(24):7189-7198.
  7. Clin Cancer Res. 2013 Mar 1;19(5):1044-53.
  8. Annu Rev Immunol. 2010;28:57-78.
Back to top