Successful human trial: Scientists program cancer-fighting T cells that self-replicate

In a landmark clinical trial, a team of UCLA scientists has successfully used a patient's own reprogrammed stem cells to create a persistent, internal factory for cancer-killing immune cells. The study, published in Nature Communications, describes a novel “tandem” therapy that could solve one of the biggest challenges in cancer immunotherapy — the short-lived effectiveness of T-cell treatments.

Current T-cell therapies often provide a powerful initial response, but the engineered cells can become exhausted and lose their function over time. The new UCLA approach, tested in a Phase I clinical trial, combats this by using two separate cell infusions. Patients first receive a standard infusion of T cells engineered to attack tumors with the NY-ESO-1 antigen. A day later, they receive a second infusion of their own genetically modified blood-forming cell, formally called hematopoietic stem cells (HSCs).

These HSCs act as a long-term, self-renewing source, generating new T cells directly inside the body. Crucially, the paper reports that these new T-cell “progeny” showed tumor-specific functionality with “no evidence of anergy or exhaustion,” directly addressing the primary weakness of existing therapies.

We’ve shown that it’s possible to reprogram a patient’s own stem cells to create a renewable immune defense against cancer. It’s not a cure yet... but it points to a future where we don’t just treat cancer — we prevent it from coming back. — Dr. Theodore Scott Nowicki, a lead author of the study.

The engineered stem cells also include a built-in safety feature: a “suicide gene” called sr39TK. This gene allows doctors to track the cells in the body using PET scans and provides a way to destroy them if any unexpected toxicity occurs.