iPSCs Used To Develop Cell Therapies for Colorectal Cancer

In recent years, adoptive cell transfer therapies have given cancer patients new hope and, in some cases, even cures. In these therapies, anti-cancer cells are processed and injected into patients. A new study by the Shin Kaneko Laboratory shows how iPS cells can be used to prepare even more potent adoptive cell transfer therapies for colorectal cancers.

In typical adoptive cell transfer therapies, the anti-cancer cells are taken directly from the patient. In all cases of cancer, the patient produces tumor-infiltrating lymphocytes that recognize and kill cancer cells. The problem is that the number of these lymphocytes is not high enough to stop the cancer from spreading.

CiRA Prof. Shin Kaneko explains that because of the recognition, most adoptive cell transfer therapies use these cells.

"The cells are collected and expanded, but the cells lose their potency. The ideal cells for the therapy would have juvenile properties. This means longer persistency and more proliferation. But these conditions are difficult to manufacture if using patient cells," he said.

Kaneko added that along with these properties is that the lymphocytes target the cancer cells with high specificity. That is, they kill cancer cells but no healthy cells in the patient. iPS cells can provide the juvenile properties, but only certain iPS cells can also provide the specificity.

"Our hypothesis was that we could maintain the cancer specificity if we programmed tumor-infiltrating lymphocytes. Other reprogrammed cells would not have specificity," said Takeshi Ito, the first author of the study.

Unlike other iPS cells, those made from reprogrammed tumor-infiltrating lymphocytes carried the surface receptors needed to recognize the cancer cells. To test their hypothesis, the researchers collected tumor-infiltrating lymphocytes sensitive for colorectal cancers. These cells were then reprogrammed into iPS cells and then differentiated back into tumor-infiltrating lymphocytes.

Notably, in contrast to the original tumor-infiltrating lymphocytes, those differentiated from iPS cells showed longer telomeres and persistency and more proliferation, resulting in superior cytotoxicity against the cancer cells.

"In adoptive cell transfer therapies, patient cells are safest but not always effective at killing the cancer. We are developing safe adoptive cell transfer therapies with iPS cells that have a higher killing effect," said Kaneko.

Reference: Ito T, Kawai Y, Yasui Y, et al. The therapeutic potential of multiclonal tumoricidal T cells derived from tumor infiltrating lymphocyte-derived iPS cells. Commun Biol 2021;4:694. doi: 10.1038/s42003-021-02195-x

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