Immune-oncology research is greatly stimulated by the clinical success of immune checkpoint modulators which lead to the identification of new tumor immunology targets. However, drug development and assessment of immune checkpoint modulators need appropriate preclinical immune-oncology models. To this end, TIGIT has held the spotlight as a new immune checkpoint receptor target. Creative Biolabs, a leader in the industry of antibody and animal models, always focus on the research highlight of onco-immunology studies. Currently, we are proud to provide you this innovative humanized TIGIT immune checkpoint knock-in mice with extensive experience and legendary transgenic techniques.

TIGIT Immune Checkpoint Receptor

TIGIT (also known as T cell immunoreceptor with Ig and ITIM domains) is identified as a co-inhibitory molecule belongs to the PVR family of immunoglobulin (Ig) proteins. It is composed of an extracellular immunoglobulin variable-set (IgV) domain, an intracellular domain with a canonical immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoglobulin tyrosine tail (ITT) motif. The poliovirus receptor (PVR or CD155) is considered as the ligand of TIGIT with high affinity and PVRL2 (Nectin2 or CD112) binds to TIGIT with a weaker binding capacity.

Inhibition of the cancer immunity cycle by TIGIT (Manieri et al. 2016) Fig.1 Inhibition of the cancer immunity cycle by TIGIT (Manieri et al. 2016)

The cancer immunity cycle refers to the processes involved in developing an immune response to kill cancer cells by proper means. In short, dendritic cells capture antigen from dying cancer cells and then migrate to lymph nodes to prime T cells, activated T cells migrate back into tumors and recognize peptide-MHC to kill tumor cells, and then the cycle can continue again.

On cytotoxic T cells or NK cells, the interaction of TIGIT with either of its ligands are able to inhibit immune cells at multiple steps in the cancer immunity cycle (see Fig.1):

  • Firstly, TIGIT can inhibit NK cell effector function by preventing initial tumor cell death and release of cancer cell antigens;
  • Secondly, TIGIT suppress dendritic cell co-stimulatory abilities and increased anti-inflammatory cytokines such as IL-10;
  • Thirdly, TIGIT+ Tregs or PVR-stimulated myeloid cells could suppress the function of CD8+ T cell effector or the polarization of skew CD4+ T cell;
  • Finally, TIGIT can directly inhibit CD8+ T cell effector function or TIGIT+ Tregs can inhibit CD8+ T cells and prevent elimination of cancer cells.

Scientists are actively developing therapeutic monoclonal antibodies to TIGIT checkpoint regulator. Antibodies that block TIGIT-CD155 interaction have been shown to prevent TIGIT' s function in repressing NK cytotoxicity, and further to decrease tumor growth.

Humanized TIGIT Immune Checkpoint Knock-In Mice

Development of TIGIT Immune Checkpoint Knock-In Mice

Ideal in vivo model for evaluating anti-TIGIT drugs requires 1) native-like TIGIT expression; 2) highly mimic tumor microenvironment; 3) potent body immune system that can elicit obvious effects. Conventional immunodeficient mouse models fail to meet these demands as the immune system is compromised. By contrary, our Magic™ humanized TIGIT knock-in mice can make an excellent model for immunotherapy investigation, with high reliability and accuracy.

Creative Biolabs spares no efforts developing a wide range of world-class Humanized Immune Checkpoint Mouse Models, not limited to TIGIT. All of our humanized mouse models are fully validated with treatment data and immunoprofiling, providing adequate quality assurance.

Meanwhile, we can also provide a broad range of immune checkpoint mouse models, including but not limited to:

Besides, we provide a variety of other Humanized Mouse Models you may be interested in:

Our diligent scientists are always ready to deliver professional services 24/7. Please feel free to contact us for more details.

References

  1. Manieri N A, Chiang E Y, Grogan J L. (2017). TIGIT: A key inhibitor of the cancer immunity cycle. Trends in immunology, 38(1), 20-28.
  2. Stanietsky N, Simic H, Arapovic J, et al. (2009). The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proceedings of the National Academy of Sciences, 106(42), 17858-17863.

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