Can We Reactivate T Cells After TCR-T Therapy Stops Working?
A new pilot trial at Northwestern University is asking one of the most important questions in synovial sarcoma treatment: when TCR-T therapy stops working, are the T cells truly gone, or can they be brought back to life?
Background: The Promise and the Limit of TCR-T Therapy
TCR-T cell therapy represents a major advance for patients with synovial sarcoma and myxoid/round cell liposarcoma (MRCL). In some clinical trials, approximately 40–50% of patients with synovial sarcoma or myxoid/round cell liposarcoma have responded to TCR-T therapy. However, many patients eventually experience disease progression, often within the first two years.
When cancer progresses after TCR-T therapy, it may seem that the engineered T cells have stopped working or disappeared. However, research has shown that some of these cells can remain in the body even after the cancer begins growing again.
New research suggests that is not always the case.
What the Research Shows
Scientists have found that even after cancer progresses following TCR-T therapy, many patients still have detectable engineered T cells circulating in their blood.
These cells have a distinctive profile. They may lack certain markers commonly associated with T-cell exhaustion, such as PD-1 and LAG-3, but appear to have limited cancer-fighting activity. Laboratory studies suggest they may still have the potential to be reactivated and begin attacking cancer cells again. Researchers call these rare persisting cells, or RPCs.
Researchers call these rare persisting cells, or RPCs.
Laboratory studies have shown that a protein called IL-15 can wake these cells up — causing them to multiply and resume killing tumor targets. Animal studies have supported the same finding. The question now is whether this can work in patients.
The Trial: NCT07261657
The trial is led by Dr. Seth Pollack, MD, Steven T. Rosen Professor of Cancer Biology and Director of the Sarcoma Program at the Lurie Cancer Center, Northwestern University Feinberg School of Medicine. Dr. Pollack is among the leading researchers in TCR-T cell therapy for sarcoma and serves on the SSF Medical Advisory Board. His team opened the pilot trial in April 2026.
The trial is testing a drug called N-803, an IL-15 superagonist manufactured by ImmunityBio. N-803 is designed to stimulate the immune system in a similar way to IL-15, but with greater potency and longer-lasting effects. The goal is to reactivate the engineered T cells that remain in patients after their cancer progresses.
Researchers will primarily evaluate the safety of N-803 and whether it can increase the number of these remaining T cells. They will also look for early signs of cancer-fighting activity, including changes in tumor size and how long patients go without further disease progression.
The study plans to enroll eight patients between the ages of 18 and 80 with synovial sarcoma or MRCL who previously received TCR-T therapy, experienced clinical benefit, but subsequently developed progressive disease. Additional eligibility and screening requirements apply. As of late August 2026, three patients had enrolled.
The trial is funded in part by the Waterton-Adrienne Smith Sarcoma Research Fund. ImmunityBio is supplying N-803.
Why This Matters
As TCR-T therapies become more accessible to synovial sarcoma patients — including through TECELRA, which received FDA approval in 2024 — the field faces a new challenge: what comes next when those therapies stop working?
This trial is one of the first efforts to address that question directly. Rather than moving on to an entirely different treatment, it asks whether we can extend the benefit of what patients have already received.
The answers are still ahead. This is an early-phase study, and no efficacy or safety results have been reported yet. But the scientific rationale is grounded in real biological evidence, and the implications could extend well beyond synovial sarcoma.
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