TIGIT-activating antibodies to calm autoimmune attacks in the brain and spinal cord during PD‑1 cancer therapy
Project 2: Elucidating how TIGIT agonists regulate CNS autoimmunity exacerbated by PD-1 blockade
['FUNDING_P01'] · YALE UNIVERSITY · NIH-11331997
This project is testing whether turning on the TIGIT immune 'brake' can reduce brain and spinal cord autoimmune attacks that may be worsened by PD‑1 cancer treatments.
Quick facts
| Phase | ['FUNDING_P01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | YALE UNIVERSITY (nih funded) |
| Locations | 1 site (NEW HAVEN, UNITED STATES) |
| Trial ID | NIH-11331997 on ClinicalTrials.gov |
What this research studies
This work uses laboratory and animal models to study how two immune pathways (PD‑1 and TIGIT) interact to control harmful immune responses in the central nervous system. Researchers will use a mouse model of multiple sclerosis and give PD‑1 blocking antibodies with or without TIGIT-activating antibodies to see whether TIGIT reduces disease and how regulatory CD4+ T cells respond. They will analyze immune cells, molecular signals, and tissue inflammation to map the cellular circuits behind these effects and check that TIGIT activation does not block PD‑1's tumor-fighting benefits. The project builds on in vitro human Treg data and is led by teams at Yale to inform possible future patient treatments.
Who could benefit from this research
Good fit: Ideal candidates for future clinical testing would be people with central nervous system autoimmune diseases, such as multiple sclerosis, particularly those who develop neurological immune-related side effects while on PD‑1 checkpoint inhibitor therapy.
Not a fit: Patients with non-immune neurological conditions or autoimmune disorders driven by unrelated immune pathways are unlikely to benefit from TIGIT-targeted approaches.
Why it matters
Potential benefit: If successful, this work could lead to treatments that prevent or reduce neurological autoimmune flare-ups linked to PD‑1 cancer immunotherapy and may inform therapies for diseases like multiple sclerosis.
How similar studies have performed: Preclinical studies, including mouse EAE experiments and in vitro human Treg work, have shown promising effects of TIGIT agonists on regulatory T cell function and disease reduction, but clinical testing in patients remains novel.
Where this research is happening
NEW HAVEN, UNITED STATES
- YALE UNIVERSITY — NEW HAVEN, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: SHARPE, ARLENE H. — YALE UNIVERSITY
- Study coordinator: SHARPE, ARLENE H.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions: Autoimmune Diseases