Researchers in Japan have for the first time shown it is possible to make cancer-specific immune system cells from induced pluripotent stem cells (iPSCs). Their work brings closer the day when therapies use cloned versions of patients’ own cells to boost their immune system’s natural ability to kill cancer cells.
The researchers, from the RIKEN Research Centre for Allergy and Immunology in Yokohama, describe how they created cancer-specific killer T lymphocytes from iPSCs, in a paper published online on 3 January in the journal Cell Stem Cell.
Hiroshi Kawamoto and colleagues started with mature T lymphocytes specific for a certain type of skin cancer and reprogrammed them into IPSCs with the help of “Yamanaka factors”. The iPSCs cells then generated fully active, cancer-specific T lymphocytes.
Yamanaka factors are named after Shinya Yamanaka, who with British scientist John B. Gurdon, won the 2012 Nobel Prize for Physiology or Medicine for discovering that mature cells can be reprogrammed to become pluripotent stem cells.
Yamanaka discovered that treating adult skin cells with four pieces of DNA (the Yamanaka factors) makes them revert back to their pluripotent state, where they have the potential, almost like embryonic stem cells, to become virtually any cell in the body.
Speaking about their breakthrough in making cancer-specific T cells, Kawamoto says in a statement:
“We have succeeded in the expansion of antigen-specific T cells by making iPS cells and differentiating them back into functional T cells.”
Previous attempts using conventional methods to make cancer-killing T lymphocytes in the lab have not been very successful. The cells failed to kill the cancer cells, mainly because they did not live long enough.
So Kawamoto and colleagues thought they would have more success if they went down the iPSC route.
After making a batch of iPSCs by exposing melanoma-specific mature T lymphocytes to the Yamanaka factors, they grew them in the lab and coaxed them to differentiate into killer T lymphocytes again.
“In this study, we established iPSCs from mature cytotoxic T cells specific for the melanoma epitope MART-1,” they write.
They showed that the new batch of T lymphocytes was specific for the same type of melanoma as the original lymphocytes.
The new cells kept the same genetic structure that enabled them to express the cancer-specific receptor on their surfaces: “more than 90% of the resulting cells were specific for the original MART-1 epitope,” note the researchers.
They also showed that the new T lymphocytes were active and able produce the anti-tumor compound interferon-gamma when exposed to antigen-presenting cells.
Kawamoto and colleagues are now planning to test whether the new T cells can selectively kill tumor cells without harming healthy cells.
“If they do, these cells might be directly injected to patients for therapy. This could be realized in the not-so-distant future,” says Kawamoto.
Written by Catharine Paddock PhD