Off-the-shelf and mass-producible immune cells have been shown to fight solid human tumors engrafted into mice, according to a Jul. 23 report from Kobe University. The development is described as a significant contribution toward faster and less expensive cancer immunotherapy.
The body's immune system uses T cells as one of its main defenses against cancer. Modern cancer immunotherapies often target these T cells, enhancing their ability to locate and destroy cancerous cells. Traditional techniques require extracting a patient's own T cells, modifying them in the laboratory, and reintroducing them into the patient—a process that is both costly and time-consuming.
Researchers have explored using gamma-delta (γδ) T cells, which do not need to be customized for each individual but can be harvested from donors for use in other patients. However, these γδ T cells are rare and difficult to multiply directly in the lab.
AOI Takashi, a stem cell researcher at Kobe University, said, "Based on our experience with induced pluripotent stem cells, also called iPS cells, we thought that we could approach this issue by creating such easily storable and growable cells from these specific T cells, and then only turning them back into T cells when actually needed." He explained that because T cell DNA adapts during development to target specific threats, creating iPS cells from cancer-specific T cells ensures all descendants retain this specificity—essentially producing many identical copies of an effective cancer-fighting cell.
In their recent paper published in Stem Cell Reports, Aoi's team demonstrated they could create iPS cells from γδ T cell subclasses usable across patients. They were able to reproducibly turn these back into functional γδ T cells with an overall 80,000-fold multiplication rate without relying on animal products—a requirement for clinical applications. The study was also the first small-scale preclinical demonstration showing that these engineered T cells attacked and shrank human colorectal cancer tumors implanted in mice.
Futai said, "This suggests potential for future systemic therapy. We believe this achievement represents an important step toward the development of a new immunotherapy for solid tumors." However, Futai cautioned, "This study is a preclinical investigation demonstrating the potential using iPS cell-derived T cells and is not yet at a stage where it can be used on patients." Aoi concluded by saying, "Furthermore, by combining this approach with cell modification techniques such as CAR therapy, we hope that this research will eventually lead to the development of new therapeutic possibilities for patients with solid tumors."
