Why 4-1BB CAR T cells can stop working
Decoding 41BB-specific dysfunction programs in cellular immunotherapies for cancer
This project looks into why CAR T cell treatments that use the 4-1BB signal sometimes stop working for people with B‑cell leukemias and lymphomas.
Quick facts
| Grant type | R37 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11247957 on NIH RePORTER |
What this research studies
Researchers are mapping the molecular programs that make CAR T cells lose function after long-term activation. They use lab models that mimic chronic CAR stimulation and compare 4-1BB versus CD28 costimulatory designs to see how each changes T cell behavior. The team examines human-derived T cells with molecular profiling to find specific genes and pathways linked to dysfunction. Findings will be used to design CAR T cells with altered signaling that may resist or reverse failure.
Who could benefit from this research
Good fit: People with B‑cell leukemias or lymphomas who are eligible for or interested in CD19-directed CAR T therapies would be the most relevant candidates for related trials or sample donation.
Not a fit: Patients with cancers that are not B‑cell leukemias/lymphomas or diseases not treated by current CAR T approaches are unlikely to benefit directly from this work.
Why it matters
Potential benefit: If successful, this work could lead to CAR T therapies that persist longer and produce more durable remissions for people with B‑cell leukemia and lymphoma.
How similar studies have performed: CD19-targeted CAR T therapies have cured some patients but durable remissions occur in fewer than half, and prior work shows costimulatory domains affect persistence while the exact failure programs remain actively studied.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Singh, Nathan — Washington University
- Study coordinator: Singh, Nathan
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.