Stanford Medicine researchers have created a method to transform natural killer cells into a tissue-resident form capable of infiltrating and destroying solid tumors.

Researchers at Stanford Medicine have developed a strategy to transform natural killer cells into specialized tissue-resident cells that can enter and attack solid tumors. By exposing these immune cells to specific signals, the team created a version capable of infiltrating tumor tissue. The study, published in Science Translational Medicine, suggests this approach could lead to off-the-shelf cancer therapies that are more accessible than current patient-specific treatments.

Optimizing Cell Function

The research team found that the signaling protein TGF-b is essential for converting natural killer cells into a tissue-resident form. However, the timing and amount of the signal are critical; prolonged exposure renders the cells dysfunctional. By briefly exposing the cells to human epithelial tumor cells, the researchers produced a version that remains highly effective at killing cancer cells.

Promising Results in Laboratory Models

In tests involving mice, the modified natural killer cells successfully slowed the growth of solid tumors, including melanoma and head and neck squamous cell carcinoma. The treatment was most effective when combined with cetuximab, an antibody that marks cancer cells for immune attack. Mice receiving the combination therapy remained healthy through the 30-day observation period.

Potential for Off-the-Shelf Therapy

Unlike current immune cell therapies that require individual manufacturing from a patient's own cells, these modified natural killer cells do not typically trigger immune reactions when transferred between people. The researchers have developed a method to produce and cryopreserve these cells, potentially allowing for large-batch production. A Phase I clinical trial for patients with advanced squamous cell carcinoma is currently being prepared.