TIGIT (T-Cell Immunoreceptor With Ig And ITIM Domains) is a co-inhibitory receptor expressed on all T-cell subtypes and NK cells. Binding of TIGIT ligands triggers a negative signal in T cells and NK cells, preventing their activation. TIGIT expression in effector and regulatory T cells is markedly enhanced in the tumor microenvironment. TIGIT expression in regulatory T cells marks a highly suppressive population.
The inhibitory role of TIGIT on immune cells is also mediated in part by competition for binding of the same ligands to the T cell and NK cell co-stimulatory molecule CD226.
TIGIT is a negative regulator of T cells and NK cells make it an attractive target for immunotherapy. Furthermore, many tumor types express TIGIT ligands and the ratio of expression for TIGIT/CD226 on T cells are modified in tumor microenvironments to TIGIT’s advantage. Administration of TIGIT blocking antibodies provides a therapeutic benefit in several murine models in monotherapy and in combination with checkpoint inhibitors. Altogether, these data give a strong rational for the development of antibody targeting TIGIT for immuno-oncology.
iTeos has selected a lead antibody, which will enter a Phase I clinical trial in the second half of 2019.