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 potential of these tissue-resident natural killer cells. When tested in mice, these cells slowed the growth of various solid tumors, including those derived from human melanoma and head and neck squamous cell carcinoma. The therapy's effectiveness was further enhanced when combined with an antibody treatment, cetuximab, which helps target cancer cells for destruction.
One of the key advantages of this approach is the ability to produce the therapy in bulk. Unlike most immunotherapies, which are personalized and created from each patient's cells, these supercharged natural killer cells can be produced in large quantities, frozen, and administered to any patient in need. This makes cell therapy more accessible and cost-effective.
The research team, led by John Sunwoo, isolated circulating natural killer cells from human blood donors and exposed them to different cellular signals, or 'recipes'. They discovered that a specific combination of signals, including TGF-b, was crucial for transforming natural killer cells into tissue-resident cells with strong toxic activity against malignant cells. This 'Goldilocks' approach ensures that the cells are not inhibited or dysfunctional.
The study revealed two distinct types of tissue-resident natural killer cells, both expressing surface proteins CD49a and CD103. However, only the efficient killers expressed CD39 and were better equipped with tools for cell death, such as perforin and granzyme A. This discovery provides valuable insights into the development and function of these cells.
The researchers' findings have significant implications for cancer treatment. By controlling tumor growth and combining the therapy with cetuximab, they achieved remarkable results in mice. The combination therapy suppressed tumors more effectively than either treatment alone, and the mice showed no adverse effects.
Sunwoo and his team are now planning a Phase I clinical trial of the combination therapy in patients with advanced squamous cell carcinoma. They have also developed a scalable method to transform and multiply the supercharged natural killer cells, making the therapy more accessible and efficient.
This breakthrough in cell therapy offers a promising approach to treating solid tumors, and the potential for off-the-shelf cell therapy could revolutionize the field of cancer treatment.
