TIGIT Antagonist Monoclonal Antibody

  • TIGIT (T-cell Immunoreceptor with Ig and ITIM domains) is a co-inhibitory receptor expressed on all T-cell subtypes, including regulatory T cells (Tregs), and NK cells. TIGIT ligands are highly expressed on tumor cells, which therefore prevents immune cells from recognizing and attacking the tumor. Administration of TIGIT antagonistic antibodies prevents cancer-mediated immune suppression and provides a therapeutic benefit in several mouse models of cancer, both as a monotherapy and in combination with other checkpoint modulators. 
  • This anti-tumoral effect is increased with ADCC-enabling TIGIT antibody.
  • In February 2020, Genentech announced the start of 8 pivotal phases 3 combining its ADCC-enabling TIGIT antibody (tiragolumab) after positive phase 2 clinical trial combining atezolizumab with tiragolumab in first line non small cell lung cancer patients.
  • EOS-448, iTeos’s clinical candidate antibody, entered a Phase I clinical trial in February 2020.
Tigit

EOS-448 prevents immunosuppression and restores antitumor immunity:

  1. Restore T/NK-cell activity by blocking CD155/CD112-mediated immunosuppression
  2. Allow engagement of CD226 costimulatory by CD155
  3. Deplete tumor cells (heme malignancies) and immunosuppressive Treg that have the highest expression of TIGIT
  4. Increase local inflammation by engaging Fcγ receptor on effector cells