Using a new immune protein to help melanoma that resists current immunotherapies

Project 3. Overcoming Melanoma Treatment Resistance with Cytokine Immunotherapy

['FUNDING_OTHER'] · YALE UNIVERSITY · NIH-11181037

This project tries a modified immune protein called DR18 to help people whose melanoma did not respond to or stopped responding to checkpoint inhibitor treatments.

Quick facts

Phase['FUNDING_OTHER']
Study typeNih_funding
SexAll
SponsorYALE UNIVERSITY (nih funded)
Locations1 site (NEW HAVEN, UNITED STATES)
Trial IDNIH-11181037 on ClinicalTrials.gov

What this research studies

If you have melanoma that stopped responding to checkpoint blockers, this work tries an engineered immune protein called DR18 to reawaken tumor-fighting cells. DR18 is designed to resist a natural blocker (IL-18BP) that limited earlier IL-18 drugs and to activate CD8 T cells and natural killer cells. It has shown promise in lab and animal models and a clinical-grade version is being developed for human testing, including an early first-in-human trial. Researchers plan to test DR18 alone and in combination with anti-PD-1 drugs to try to overcome treatment resistance in advanced melanoma.

Who could benefit from this research

Good fit: People with unresectable or metastatic melanoma who have not responded to, or who later progressed on, immune checkpoint inhibitors are the most likely candidates.

Not a fit: Patients with early-stage melanoma already cured by surgery, those with cancers other than melanoma, or individuals with medical conditions that make immunotherapy unsafe are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could restore immune control over tumors and improve responses for patients with melanoma that is resistant to current checkpoint therapies.

How similar studies have performed: Previous trials of recombinant IL-18 failed because of a natural blocker (IL-18BP), so this decoy-resistant version is a novel approach that showed positive results in preclinical studies and is now entering early human testing.

Where this research is happening

NEW HAVEN, 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.

View on NIH RePORTER →

Last reviewed 2026-05-15 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.