B-hTIGIT mice

Basic Information

Targeting Strategy

Gene targeting strategy for B-hTIGIT mice. The exon 2 of mouse Tigit gene that encodes the extracellular domain was replaced by human TIGIT exon 2 in B-hTIGIT mice.

Publications

A novel human anti-TIGIT monoclonal antibody with excellent function in eliciting NK cell-mediated antitumor immunity

Details

Phenotype

mRNA expression analysis

Strain specific analysis of TIGIT gene expression in WT and hTIGIT mice by RT-PCR. Mouse Tigit mRNA was detected in splenocytes of wild-type (+/+). Human TIGIT mRNA was detected only in homozygous B-hTIGIT mice (H/H), but not in WT mice.

Protein Expression Analysis

Strain specific TIGIT expression analysis in homozygous B-hTIGIT mice by flow cytometry.

Splenocytes were collected from WT and homozygous B-hTIGIT (H/H) mice stimulated with anti-CD3ε in vivo (7.5 µg/mice), and analyzed by flow cytometry with species-specific anti-TIGIT antibody. Mouse TIGIT was exclusively detected in WT mice. Human TIGIT were exclusively detected in homozygous B-hTIGIT mice (H/H) but not WT mice.

Application

In vivo efficacy of anti-human TIGIT antibody

Antitumor activity of anti-human TIGIT antibody in B-hTIGIT mice.

(A) Anti-human TIGIT antibody inhibited MC38 tumor growth in B-hTIGIT mice. Murine colon cancer MC38 cells (5ⅹ10⁵) were subcutaneously implanted into homozygous B-hTIGIT mice (male, 4-6 week-old, n=5). Mice were grouped when tumor volume reached approximately 150±50 mm³, at which time they were treated with anti-human TIGIT antibody and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human TIGIT antibody was efficacious in controlling tumor growth in B-hTIGIT mice, demonstrating that the B-hTIGIT mice provide a powerful preclinical model for in vivo evaluation of anti-human TIGIT antibodies. Values are expressed as mean ± SEM

In vivo efficacy of Tiragolumab(in house)

Antitumor activity of anti-human TIGIT antibodies in B-hTIGIT mice.

(A) Anti-human TIGIT antibodies inhibited MC38 tumor growth in B-hTIGIT mice. Murine colon cancer MC38 cells (5ⅹ10⁵) were subcutaneously implanted into homozygous B-hTIGIT mice (female, 8 week-old, n=6). Mice were grouped when tumor volume reached approximately 150±50 mm³, at which time they were treated with anti-human TIGIT antibodies with different doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human TIGIT antibodies were efficacious in controlling tumor growth in B-hTIGIT mice, demonstrating that the B-hTIGIT mice provide a powerful preclinical model for in vivo evaluation of anti-human TIGIT antibodies. Values are expressed as mean ± SEM

In vivo efficacy of anti-human TIGIT antibodies

Antitumor activity of anti-human TIGIT antibodies in B-hTIGIT mice.

(A) Anti-human TIGIT antibodies inhibited MC38 tumor growth in B-hTIGIT mice. Murine colon cancer MC38 cells (1ⅹ10⁶) were subcutaneously implanted into homozygous B-hTIGIT mice (female, 7 week-old, n=7). Mice were grouped when tumor volume reached approximately 150±50 mm³, at which time they were treated with two anti-human TIGIT antibodies and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, anti-human TIGIT antibodies were efficacious in controlling tumor growth in B-hTIGIT mice, demonstrating that the B-hTIGIT mice provide a powerful preclinical model for in vivo evaluation of anti-human TIGIT antibodies. Values are expressed as mean ± SEM

References

1. J Clin Invest. 2015 May;125(5):2046-58. doi:10.1172/JCI80445. Epub 2015 Apr 13.
2. Immunol Rev. 2017 Mar;276(1):112-120. doi:10.1111/imr.12518.
3. Cancer Cell. 2014 Dec 8;26(6):923-937. doi:10.1016/j.ccell.2014.10.018. Epub 2014 Nov 26.
4. J Exp Med. 2015 Nov 16;212(12):2165-82. doi:10.1084/jem.20150792. Epub 2015 Nov 9.