TIGIT Targeting

Immuno-oncology

TIGIT targeting

TIGIT is upregulated on T cells, regulatory T cells (Tregs) and natural killer (NK) cells in the tumor microenvironment (TME) of some tumor types. It inhibits their activity and prohibits CD226-mediated immune activation. TIGIT expression is a marker of exhausted T cells and immunosuppressive Tregs in the TME.1-9

M6223 – anti-TIGIT monoclonal antibody (mAb)

M6223 is an investigational fully-human IgG1 anti-TIGIT antibody with Fc effector function.10,11

This investigational compound has not been approved by any health authority. Safety and efficacy have not been established.

Fc, fragment crystallizable; IgG1, immunoglobulin G1; mAb, monoclonal antibody; NK, natural killer; PD-L1, programmed death-ligand 1; TIGIT, T-cell immunoglobulin and

ITIM domain; TME, tumor microenvironment; Tregs, regulatory T cells.

  1. Harjunpää H, Guillerey C. TIGIT as an emerging immune checkpoint. Clin Exp Immunol. 2019;200(2):108-119. 
  2. Johnston RJ, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell. 2014;26(6):923-937. 
  3. Wang F, Hou H, Wu S, et al. TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals. Eur J Immunol. 2015;45(10):2886-2897. 
  4. Chauvin J-M, Pagliano O, Fourcade J, et al. TIGIT and PD-1 impact tumor antigen-specific CD8+ T cells in melanoma patients. J Clin Invest. 2015;125(5):2046-2058. 
  5. Kurtulus S, Sakuishi K, Ngiow S-F, et al. TIGIT predominantly regulates the immune response via regulatory T cells. J Clin Invest. 2015;125(11):4053-4062. 
  6. Kim HR, Park HJ, Son J, et al. Tumor microenvironment dictates regulatory T cell phenotype: unregulated immune checkpoints reinforce suppressive function. J Immunother Cancer. 2019;7(1):339. 
  7. Fuhrman CA, Yeh W-I, Seay HR, et al. Divergent phenotypes of human regulatory T cells expressing the receptors TIGIT and CD226. J Immunol. 2015;195(1):145-155. 
  8. Joller N, Lozano E, Burkett PR, et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity. 2014;40(4):569-581. 
  9. Fourcade J, Sun Z, Chauvin J-M, et al. CD226 opposes TIGIT to disrupt Tregs in melanoma. JCI Insight. 2018;3(14):e121157. 
  10. Merck Healthcare Pipeline. Accessed December 1, 2023. Available at: https://www.merckgroup.com/en/research/healthcare-pipeline.html 
  11. TIGIT Inhibitor M6223 (Code C173891). NCI Thesaurus.nci.nih.gov. Accessed December 1, 2023. https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C1738

GL-MULO-00163 | January 2024