B-hPD-1/hTIGIT mice

Basic Information

Targeting Strategy

Details

Phenotype

mRNA Expression Analysis

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

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

Protein Expression Analysis

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

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

Application

Combination therapy of TIGIT (Tiragolumab Analog) mAb and PD-1 mAb

Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hTIGIT mice. Mice were grouped when the tumor size was approximately 150±50 mm³ (n=6). Anti-hTIGIT antibody and the anti-hPD-1 antibody Keytruda shows obviously inhibitory effects respectively. Combination of anti-hTIGIT antibody and the anti-hPD-1 antibody Keytruda shows better inhibitory effects than single treatment, suggesting that B-hPD-1 /hTIGIT mouse is a powerful tool for in vivo evaluating combination therapy efficacy of hPD-1 antibodies and hTIGIT antibodies . (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

Combination Therapy of hTIGIT Ab and PD-1 Ab

Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hTIGIT mice. Mice were grouped when the tumor size was approximately 150±50 mm3 (n=6). The human TIGIT antibody inhibits tumor growth, but Combination of hTIGIT antibody and the hPD-1 antibody Keytruda didn’t show better effects, the reason may be that the dose of PD-1 antibody is not suitable.(A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.

Publications using B-hPD-1/hTIGIT mice

1. Han D, Xu Y, Zhao X, Mao Y, Kang Q, Wen W, Yu X, Xu L, Liu F, Zhang M, Cui J, Wang Z, Yang Z, Du P, Qin W. A novel human anti-TIGIT monoclonal antibody with excellent function in eliciting NK cell-mediated antitumor immunity. Biochem Biophys Res Commun. 2021 Jan 1;534:134-140. doi: 10.1016/j.bbrc.2020.12.013. Epub 2020 Dec 16. PMID: 33341068.

References

1. Journal of Biomedical Science (2017) 24:26 doi: 10.1186/s12929-017-
   0329-9
2. J Clin Invest. 2015;125(5):2046–2058. doi:10.1172/JCI80445
3. Cancer Cell (2014), http://dx.doi.org/10.1016/j.ccell.2014.10.018