Focused ultrasound plus CD40 immune therapy to reprogram 'cold' melanoma tumors

Role of histotripsy synergized CD40 signaling in the re-engineering of cold tumors

NIH-funded research Ut Southwestern Medical Center · NIH-10895340

This project combines a noninvasive focused ultrasound treatment with a long-lasting CD40 immune booster to help people with hard-to-treat 'cold' metastatic melanoma respond better to immunotherapy.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionUt Southwestern Medical Center NIH-funded
Lab location1 site (Dallas, United States)
Project IDNIH-10895340 on NIH RePORTER

What this research studies

From a patient's perspective, researchers are using a focused ultrasound method called histotripsy to break up tumor tissue and release cancer proteins that the immune system can see. They pair this with tiny polymer particles placed into the tumor that slowly deliver an antibody that activates immune helper cells through CD40 signaling. In mouse melanoma models, this combination is given with immune checkpoint drugs to try to cause regression of both the treated tumor and distant untreated tumors. The team will optimize how the particles are made, how they are injected, and how the ultrasound and immune drugs are timed to produce durable remissions.

Who could benefit from this research

Good fit: Ideal candidates would be people with advanced or metastatic melanoma characterized as poorly immunogenic ('cold' tumors), especially when one or more tumors are accessible for an intratumoral injection and focused ultrasound treatment.

Not a fit: Patients without melanoma, with tumors that cannot be safely reached for intratumoral delivery, or whose disease already responds well to existing immunotherapies are unlikely to benefit from this specific approach.

Why it matters

Potential benefit: If successful, this approach could make immunotherapy work for patients whose melanomas are currently immune‑cold and resistant, potentially shrinking treated and untreated tumors.

How similar studies have performed: Preclinical mouse experiments by the team showed promising results, including remission of untreated tumors when the ultrasound, CD40 particles, and checkpoint drugs were combined, but human clinical evidence is not yet available.

Where this research is happening

Dallas, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.