May 23, 2017
Keio University School of Medicine
Japan Agency for Medical Research and Development (AMED)
A group led by Professor Akihiko Yoshimura of the Keio University School of Medicine and a group from Takeda Pharmaceutical Company, as part of the Innovative Advanced Research and Development Support Program of the Japan Agency for Medical Research and Development (AMED), have developed a technology to rejuvenate and reactivate exhausted immune cells (T cells) and have successfully applied it to more effective cancer treatments.
Adoptive cell transfer therapy is a treatment in which cancer-specific T cells, isolated from a cancer patient's tumor tissue, are cultured in large quantities in vitro and then transferred back into the patient. However, many of the T cells that accumulate in cancer tissues become exhausted due to repeated stimulation. They also enter a state of exhaustion through long-term cultivation. A problem with this approach has been that when these exhausted T cells are returned to the patient's body, their ability to attack cancer cells is weakened, and sufficient therapeutic effects cannot be achieved.
The research group discovered that by applying a special stimulation called Notch to cancer-specific T cells, they could convert exhausted T cells into a rejuvenated state—that is, a state similar to a naive state before being exposed to an antigen and activated. These cells possess properties of both stem cells and memory cells, proliferate rapidly upon restimulation, and are capable of long-term survival. The group also confirmed that these cells can be generated from human T cells and exhibit potent antitumor effects. The research group has named these cells "inducible T-cell stem cell memory (iTSCM)."
This achievement makes it possible to expand T cells that specifically react to cancer without using gene transfer technology, and it is expected to be applicable to cancer treatment in the near future. It is also anticipated to lead to the development of methods for cellular "rejuvenation" and the elucidation of its mechanisms, not limited to immune cells.
The results of this research were published in the online advance publication of the British scientific journal "Nature Communications" on May 22, 2017 (UK time).
For the full press release, please see below.