A Fail-Safe Suicide Switch For iPSC Cancer Therapy

By introducing the suicide gene iCaspase-9 into induced pluripotent stem cells, scientists are now able to prevent the formation of tumors should the cells go rogue.

AsianScientist (Sep. 3, 2015) – Researchers at the University of Tokyo introduced a safeguard system for induced pluripotent stem cell (iPSC) therapy in the treatment of cancer. Their method allowed on-demand killing of iPSC introduced in the therapy, lowering the chance of iPSC-induced tumor growth. This finding, published in Stem Cell Reports, will accelerate research towards realizing clinical applications of iPSC therapy in the treatment of cancer.

In 2013, Professor Hiromitsu Nakauchi’s research group at the University of Tokyo Institute of Medical Science’s Division of Stem Cell Therapy successfully developed a technique to produce killer T-cells, a type of immune cell, in a rejuvenated state from iPSC. These rejuvenated cells could potentially be used in immunotherapies for cancers or infections. However, before this technique could be used safely in clinical settings, it was necessary to develop techniques to control the iPSC in case they became cancerous or produced other side effects.

In the present study, the same group they introduced a suicide gene, iCaspase-9, into the iPSC, which they then differentiated into the rejuvenated killer T-cells for cancer treatment. The research group confirmed that by administering a specific drug that induced cell death in the iPSC-derived T-cells, it was possible to eradicate these T-cells in mice. This demonstrates that if side effects were to appear in therapeutic use, it would be possible to eliminate the iPSC-derived T-cells in the patient.

Furthermore, they have experimentally demonstrated that rejuvenated killer T-cells effectively reduce tumor size both in vivo and in vitro in this study. Compared to ordinary T-cells, these iPSC-derived T-cells were more effective at reducing the size of a tumor implanted into a mouse, and also extended the survival time of the mouse.

This research provides a means to control any potential side effects that might occur as a result of the T-cell therapy. It greatly advances the possibility of safe and effective T-cell therapies.

Nakauchi said, “This safety mechanism can also be applied to other iPSC-derived therapies.”

The article can be found at: Ando et al. (2015) A Safeguard System for Induced Pluripotent Stem Cell-Derived Rejuvenated T Cell Therapy.

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Source: The University of Tokyo.
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