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B-hPD-1/hTIGIT mice
Strain Name C57BL/6-Pdcd1tm1(PDCD1)Tigittm1(TIGIT)/Bcgen Common Name  B-hPD-1/hTIGIT mice
Background C57BL/6 Catalog number  120523
Related Genes 
PD-1 (Programmed death-1) ;
(T-cell immunoreceptor with Ig and ITIM domains)

Gene Description

PD-1 (Programmed death-1) is mainly expressed on the surface of T cells and primary B cells. The two PD-1 ligands, PD-L1 and PD-L2, are widely expressed on antigen-presenting cells (APCs). PD-1 interacts with its ligands and plays an important role in the negative regulation of the immune response. PD-L1 protein expression is detected in many human tumor tissues. PD-L1 expression in tumor cells could be induced by the microenvironment of tumor cells. PD-L1 expression is favorable for tumorigenesis and growth, for induction of anti-tumor T Cell Apoptosis, and for escaping responses by the immune system. Inhibition of PD-1 binding to its ligand can result in tumor cells that are exposed to the killing version of the immune system, and thus is a target for cancer treatments. TIGIT (T-cell immunoreceptor with Ig and ITIM domains), a member of the immunoglobulin family of PVR (poliovirus receptor), is a type I transmembrane protein. Similar to PD-1, TIM3, and LAG3, TIGIT is highly expressed in cancer tissues and competitively binds to TIGIT receptors with DNAM-1 proteins on the surface of NK cells to reduce the NK cell killing efficiency of cancer cells. Therefore, anti-TIGIT antibody can enhance NK cell ability to destroy tumor cells by facilitating DNAM-1 binding to TIGIT receptors. It has become the new generation of cancer immunotherapy checkpoint.

Protein expression analysis

Strain specific TIGIT and PD-1 expression analysis in homozygous B-hPD-1/hTIGIT mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hTIGIT mice (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 and PD-1 were exclusively detected in WT mice. Human TIGIT and PD-1 were exclusively detected in homozygous B-hPD-1/hTIGIT mice but not WT mice.

Combination therapy of hTIGIT Ab( Tiragolumab (in house)) and PD-1 Ab(pembrolizumab) 

Antitumor activity of anti-hTIGIT antibody Tiragolumab (in house) combined with anti-hPD-1 antibody pembrolizumab in B-hPD-1/hTIGIT mice. (A) Anti-hTIGIT antibody Tiragolumab (in house) combined with anti-hPD-1 antibody pembrolizumab inhibited MC38 tumor growth in B-hPD-1/hTIGIT mice. Murine colon cancer MC38 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1/hTIGIT mice (female, 5-8 week-old, n=6). Mice were grouped when tumor volume reached approximately 150±50 mm3, at which time they were treated with anti-hTIGIT antibody Tiragolumab (in house) combined with anti-hPD-1 antibody pembrolizumab with doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, combination of anti-hTIGIT and anti-hPD-1 antibody shows more inhibitory effects than individual groups, demonstrating that the B-hPD-1/hTIGIT mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of hTIGIT antibodies and hPD-1 antibodies . Values are expressed as mean ± SEM.