Off-the-shelf, mass-producible immune cells fight human solid tumors transplanted into mice. Kobe University’s development will significantly contribute to faster and cheaper cancer immunotherapy.
The body mobilizes an army of immune cells to fight cancer, and one of the main forces is T cells. They are also targets of modern cancer immunotherapies, which seek to improve the ability of T cells to find and attack cancer cells. When modifying T cells, current technology requires extracting a patient’s own T cells from the blood, modifying them in the lab, and reintroducing them into the patient, which is not only extremely expensive but also consumes valuable time.
Researchers are considering focusing on a subclass of T cells called gamma delta (γδ) T cells. This subclass does not need to be tailored to individual patients and can be taken from a donor and used on others. However, these cells are much less abundant, making harvesting approaches unfeasible, and cannot be successfully grown directly in the laboratory.
“Based on our experience with induced pluripotent stem cells, also known as iPS cells, we thought we could approach this problem by creating cells from these specific T cells that can be easily stored and expanded, and then turning them back into T cells only when actually needed,” said Takashi Aoi, a stem cell researcher at Kobe University. Because T cells modify their DNA during development to target specific threats, creating iPS cells from cancer-specific T cells also means that all their progeny retain their specificity. Essentially, this process amounts to creating an army of clones from one great cancer fighter.
In the latest paper published in the journal stem cell reportAoi and his team have shown that they can create iPS cells from subclasses of T cells that can be used across patients, and that they can be expanded 80,000 times in total and reproducibly returned to those T cells. Importantly, this was accomplished without relying on animal cells or extracts, which is a requirement for clinical applications. Their study also showed for the first time on a small preclinical scale that the resulting T cells attack and shrink colorectal cancer tumors from human patients transplanted into mice.
Cancers derived from cell culture lines do not have the same drug sensitivities as real cancers, nor do they mimic the physical barriers of real tumors. This is why patient-derived organoids are so important for evaluating new cancer treatment approaches. ”
Ryoko Nii, lead author of the study
When planning the study, the Kobe University team envisioned their approach being used to fight metastatic cancer. Therefore, they also investigated whether T cells would find their targets not only when administered close to the tumor, but also when administered intravenously a week after tumor implantation. And in fact, even in this setting, tumor weights were reduced by 43 to 92 percent in the three mice tested. Mr. Futai says: ”This suggests the possibility of future systemic therapy. We believe this result is an important step toward the development of new immunotherapies for solid tumors.”
At this stage, the study was conducted on a small scale, with only three to four mice used in each experiment, and the tumor models derived from only two different patients. This is particularly important as colorectal cancer tumors are known to be highly variable.
“This study is a preclinical study to demonstrate the possibility of using iPS cell-derived T cells, and is not yet at a stage where it can be used in patients,” Professor Nii cautions.
But by conducting further research using these easily grown, highly standardized cells, the Kobe University development could also be used to uncover where variation comes from and what steps should be taken to combat it. “Furthermore, by combining this approach with cell modification technologies such as CAR therapy, we hope that this research will ultimately lead to the development of new therapeutic possibilities for patients with solid tumors,” Professor Aoi concluded.
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Reference magazines:
Nii R. others. (2026) Allogeneic iPSC-derived γδT cells exhibit antitumor effects on patient-derived tissues. stem cell report. DOI: 10.1016/j.stemcr.2026.103018. https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(26)00229-8
