TX99 Is a Neutralizing Monoclonal Antibody Against Mouse TIGIT

Area of Science:

• Immunology
• Cancer Research
• T cell biology

Background:

• T cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory receptor on immune cells that negatively regulates anti-tumor responses.
• Blocking TIGIT is a potential cancer therapy, but studies in mouse models are limited by the lack of effective neutralizing antibodies.
• Understanding TIGIT's role in tumor immunity requires tools to study its function in preclinical models.

Purpose of the Study:

• To generate and characterize novel neutralizing monoclonal antibodies (mAbs) against mouse TIGIT (mTIGIT).
• To evaluate the potential of these mAbs for studying TIGIT-mediated tumor immunity in mouse models.
• To identify a specific anti-mTIGIT mAb capable of blocking TIGIT-ligand interactions and enhancing anti-tumor responses.

Main Methods:

• Generation of five anti-mTIGIT mAb clones (TX99, TX100, TX103, TX104, TX105).
• Assessment of antibody binding affinity to mTIGIT.
• Evaluation of antibody's ability to block TIGIT-CD155 interaction.
• Measurement of NK cell-mediated cytotoxicity against tumor cells.

Main Results:

• TX99 and TX100 demonstrated strong binding to mTIGIT.
• TX99 effectively inhibited the interaction between mTIGIT and its ligand CD155.
• TX99 treatment resulted in increased NK cell-mediated cytotoxicity against CD155-expressing tumor cells (RMA-S).

Conclusions:

• TX99 is a potent neutralizing anti-mTIGIT mAb.
• TX99 can be utilized as a valuable tool for investigating mTIGIT functions in cancer immunity.
• This antibody provides a means to explore TIGIT blockade as a therapeutic strategy in mouse tumor models.