Scientists have made significant strides in harnessing the body's immune cells to treat liquid tumors, but solid tumors have proven more elusive. Stanford Medicine researchers and collaborators have developed a novel cell therapy that could revolutionize the treatment of solid tumors. By supercharging natural killer cells, they've created a specialized form that can effectively infiltrate and destroy solid tumors.
The study, published in Science Translational Medicine, demonstrates the remarkable ability of these tissue-resident natural killer cells to penetrate solid tumors, outperforming conventional natural killer cells. John Sunwoo, MD, and his team achieved this by exposing circulating natural killer cells to specific cellular signals, including TGF-b, a multifunctional signaling protein. They discovered that a delicate balance of TGF-b is crucial for the cells to become tissue-resident and highly toxic against malignant cells.
The researchers found that short-lived human epithelial tumor cells, which present a fleeting amount of active TGF-b, produce highly efficient killers. Direct contact with these cells, rather than mere proximity, was essential for activation. This led to the identification of two distinct types of tissue-resident natural killer cells, each with unique functions and requirements.
One type, efficient killers, expressed CD39 and was better equipped with tools for cell death, such as perforin and granzyme A. The other type, immunosuppressive, was beneficial in certain situations but not in cancer treatment. The study's findings provide a 'Goldilocks' recipe for transforming natural killer cells into powerful tissue-resident cells.
When tested in mice, these supercharged natural killer cells significantly slowed the growth of various solid tumors, including those derived from human melanoma and head and neck squamous cell carcinoma. Combining them with cetuximab, a monoclonal antibody treatment, further enhanced tumor suppression. The combination therapy showed promising results without adverse effects, paving the way for a Phase I clinical trial in patients with advanced squamous cell carcinoma.
Sunwoo's team has also developed a scalable method to transform and multiply these cytotoxic tissue-resident natural killer cells, potentially making cell therapy more accessible and efficient. This breakthrough could revolutionize the treatment of solid tumors, offering a promising approach for patients in need.
