Two New TCR-NK Cell Therapy Trials Now Recruiting for Synovial Sarcoma

Two clinical trials testing TCR-NK cell therapy for advanced synovial sarcoma are now recruiting patients, one in the United States and one in the United Kingdom. Both use donor-derived natural killer cells engineered to target proteins commonly found on synovial sarcoma tumors.

What Is TCR-NK Cell Therapy?

TCR-NK therapy works differently from the TCR-T cell therapies patients may already be familiar with. Natural killer (NK) cells from healthy donors are engineered to carry a T-cell receptor (TCR), which helps the NK cells find a protein that many synovial sarcoma tumors carry. The US trial targets NY-ESO-1, and the UK trial targets MAGE-A4.

Because the cells come from donors rather than being manufactured from each patient’s own cells, they are prepared in advance instead of requiring individual cell collection and processing. In both trials, patients receive a short course of chemotherapy before the cell infusion to help the new cells take hold.

Eligibility Depends on Two Tests

Each trial accepts patients whose tumor carries the trial’s target protein and whose immune type matches. Two tests determine eligibility:

Test 1: HLA Type, a blood test that identifies your immune type. The US trial accepts HLA-A02:01, A02:05, or A02:06. The UK trial requires HLA-A02:01.

Test 2: Tumor Antigen, a test on tumor tissue showing which target protein it carries. The US trial requires NY-ESO-1. The UK trial requires MAGE-A4 positivity.

The United States Trial

Run at MD Anderson Cancer Center in Houston (NY-ESO-1 TCR/IL-15 NK, NCT06083883), this Phase I/Ib trial is recruiting patients ages 16 to 80.

Key eligibility includes:

• HLA-A02:01, A02:05, or A*02:06 positive
• NY-ESO-1 expressed in at least 50% of tumor cells, confirmed at MD Anderson
• Prior systemic therapy including doxorubicin and/or ifosfamide
• Measurable disease
• Prior cell therapy allowed after three months, but no prior NY-ESO-1 therapy

The United Kingdom Trial

Sponsored by Zelluna (ZI-MA4-1, NCT07613723), this Phase 1 trial is recruiting at The Royal Marsden in London and The Christie in Manchester, for patients ages 18 to 75.

Key eligibility includes:

• HLA-A*02:01 positive
• Tumor tests positive for MAGE-A4
• Inoperable, locally advanced or metastatic synovial sarcoma
• At least one prior line of cancer therapy
• Measurable disease
• No prior cell or gene therapy

Next Steps: Ask Your Oncologist About Testing

Talk with your oncologist about HLA and tumor antigen testing to find out whether either trial is an option for you. Full eligibility details and other synovial sarcoma trials are available at synovialsarcoma.org/clinical-trials-and-therapies.

Trial details from ClinicalTrials.gov, September 2026.