Anti-TIGIT therapies for solid tumors: a systematic review.

Area of Science:

• Immunology
• Oncology
• Drug Development

Background:

• Existing immunotherapies like PD-(L)1 and CTLA-4 inhibitors have limitations, necessitating novel approaches.
• TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is an immune checkpoint that inhibits T cells, presenting a therapeutic target.
• Preclinical data suggest TIGIT inhibition can restore anti-tumor responses and synergize with PD-1 blockade.

Approach:

• A systematic review of PubMed-referenced clinical trials for anti-TIGIT therapies was conducted.
• Phase I/II trial data for vibostolimab, etigilimab, and tiragolumab (in combination with anti-PD-1 agents) were analyzed.
• ClinicalTrials.gov was queried for ongoing and completed anti-TIGIT trials, focusing on patient populations and trial phases.

Key Points:

• Anti-TIGIT therapies, including vibostolimab and tiragolumab, are being investigated, often in combination with anti-PD-1 antibodies.
• The Phase II CITYSCAPE trial showed improved objective response rate and progression-free survival with tiragolumab plus atezolizumab in advanced NSCLC.
• Early-phase trials suggest anti-TIGIT is a safe therapeutic strategy with an acceptable toxicity profile, even with combination therapy.

Conclusions:

• Targeting TIGIT represents a safe and promising novel immunotherapy approach for cancer treatment.
• Combination therapy with anti-TIGIT and anti-PD-1 antibodies is a key area of research, particularly for advanced non-small cell lung cancer (NSCLC).
• Further clinical trials, including Phase III studies, are ongoing to validate the efficacy and safety of anti-TIGIT agents.