Changing tumor DNA packaging and environment to help the immune system spot cancer
Remodeling Chromatin and the Tumor Microenvironment: Direct Oncogenesis and Therapeutic Targeting
['FUNDING_P01'] · MASSACHUSETTS GENERAL HOSPITAL · NIH-11184336
This project tests whether blocking a protein called DDI2—using an existing HIV drug like nelfinavir—can make tumors show more antigens so the immune system and immunotherapy can better attack cancers.
Quick facts
| Phase | ['FUNDING_P01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | MASSACHUSETTS GENERAL HOSPITAL (nih funded) |
| Locations | 1 site (BOSTON, UNITED STATES) |
| Trial ID | NIH-11184336 on ClinicalTrials.gov |
What this research studies
Researchers found that the transcription factor MITF controls a protease called DDI2 that can lead to loss of MHC class I and II and reduced antigen presentation in tumors. In lab-grown cells and animal models, blocking DDI2 genetically or with the HIV protease inhibitor nelfinavir restored antigen display and increased antigen-specific T cell activation. The team is studying this mechanism across multiple solid tumor types and testing combinations with immune checkpoint drugs such as anti-PD-1. The work combines molecular studies, drug repurposing, and preclinical tumor models with the goal of moving toward treatments that improve tumor recognition by the immune system.
Who could benefit from this research
Good fit: People with solid tumors—particularly melanoma or other cancers treated with immune checkpoint therapies—would be the most likely candidates for related clinical trials.
Not a fit: Patients whose cancers do not depend on MHC-mediated antigen presentation or who cannot take the repurposed drug may not benefit from this approach.
Why it matters
Potential benefit: If successful, this approach could make tumors more visible to patients' immune systems and improve responses to existing immunotherapies, possibly using an already-approved drug.
How similar studies have performed: Similar strategies have shown promise in laboratory and animal studies, but clinical testing in patients remains novel.
Where this research is happening
BOSTON, UNITED STATES
- MASSACHUSETTS GENERAL HOSPITAL — BOSTON, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: FISHER, DAVID E — MASSACHUSETTS GENERAL HOSPITAL
- Study coordinator: FISHER, DAVID E
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.