Engineered T cells that release TNF-alpha to better attack solid tumors
Official title: TNF-alpha-"armed" TCR vectors to enhance adoptive cell therapy for solid tumors
Funded at University of California Los Angeles · NIH-11300997 · Data updated 2026-11-12
This work aims to make engineered T cells that release a helpful immune protein called TNF-alpha at the tumor site to improve treatment for people with solid cancers.
Quick facts
| Grant type | R37 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California Los Angeles NIH-funded |
| Lab location | 1 site (Los Angeles, United States) |
| Project start | March 11, 2025 |
| Project end | February 28, 2030 |
| Funding year | 2026 |
| Award (this year) | $647,632 |
| NIH project number | 5R37CA289813-02 |
| Project ID | NIH-11300997 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates would be people with solid tumors that express the specific targets used by the engineered TCR or CAR and who are eligible for adoptive cell transfer therapies.
✕Less likely to help
Patients whose tumors lack the targeted antigen, who are not eligible for cell therapy, or who have conditions that make TNF-related inflammation unsafe may not benefit from this approach.
What this research studies
You would have immune cells taken from your blood and reprogrammed to recognize your tumor and to produce TNF-alpha only when they find cancer, so they become more active inside the tumor. The team has built viral vectors that carry both a tumor-targeting receptor and TNF-alpha and seen stronger tumor-killing in lab dishes and humanized mouse models. They plan to test these TNF-armed receptors across several tumor targets to find which combinations work best. Early studies showed the extra TNF-alpha was produced in a tumor-dependent way and did not cause obvious whole-body inflammation in preclinical tests.
Why it matters
Potential benefit: If successful, this approach could make adoptive T-cell therapies work better against solid tumors that currently respond poorly to existing engineered T-cell treatments.
How similar studies have gone: While CAR/TCR cell therapies have been very successful in some blood cancers, success in solid tumors has been limited, and cytokine-armed T cells are a newer preclinical strategy with promising animal data but limited clinical testing so far.
Where this research is happening
-
University of California Los Angeles
Los Angeles, United States Active
Researchers
- Principal investigator: Nowicki, Theodore Scott — University of California Los Angeles
- Study coordinator: Nowicki, Theodore Scott
Related research
Other NIH-funded projects on the same topics.
-
Pediatric Preclinical In Vivo Testing Center for Pediatric Sarcoma and Other Solid Tumors
A program uses mouse tumor models to identify promising drug candidates for children with sarcoma and other solid tumors.
-
Engineered CAR T immune cells targeting GPC3 for children's solid tumors
Engineered CAR T immune cells that produce IL-15 and IL-21 to better find and fight GPC3-positive solid tumors in children.
-
Boosting CAR T cell power in solid tumors by turning on transcription factors
A new research project tests whether turning on specific human transcription factors can make CAR T cells work better against solid tumors.
-
Engineering CD19 mimotopes to boost and broaden CD19-CAR T cell therapy
A patient-focused look at improving existing CD19-CAR T cell therapy so more people with blood cancers might benefit.
-
Radio-triggered CAR-T cells to better control solid tumors
A new approach uses radiation to turn on and guide CAR-T cells to fight solid tumors more effectively, potentially improving local and distant tumor control for patients with cancer.
-
Understanding how cell behavior changes drive breast cancer in 3D cultures
Researchers are studying how breast cells transition toward cancer using advanced 3D cultures and patient-derived samples to uncover important cell-state changes.
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.