04 January 2013

Treating Cancer With Killer T Cells Produced From Induced Pluripotent Stem Cells (iPS)

Japanese researchers at Riken have successfully created cells that will specifically attack cancer cells. These Killer T cells or lymphocytes were developed from induced pluripotent stem cells.

Stem Cells

Stem cells are cells that can differentiate (transform) into other type of cells, usually a higher form such as tissues and organs. There are specialized stem cells such as heart stem cells or blood stem cells that differentiates into specific type of cells.

Stem cells that can differentiate into other type of cells are called pluripotent stem cells. These are usually found in human embryos and what is generally known to the public as stem cells.

Scientists have recently discovered a method to convert an adult stem cell (whose differentiation is limited to certain types of tissues/organs) into a pluripotent stem cell. These are called Induced Pluripotent Stem Cell (iPS). iPS cells are special in that it circumvents the controversy on harvesting stem cells from human embryos.

Killer T Cells

White blood cells or leukocytes are cells used by the immune system in attacking foreign and harmful cells. A subgroup of leukocytes are lymphocytes or killer t-cells.

Killer T cells are responsible for identifying and attacking infected cells. But when it comes to cancer cells, killer t-cells are not as efficient in weeding out these harmful cells. For one, some cancer cells have a property that prevents if from being attacked by killer t-cells. Another is that, lymphocytes have a short life span that proves ineffective in a prolonged fight.

Creating Killer T Cells from Induced Pluripotent Stem Cells To Treat Cancer

Researchers from the RIKEN Research Centre for Allergy and Immunology in Japan report today that they have succeeded for the first time in creating cancer-specific, immune system cells called killer T lymphocytes, from induced pluripotent stem cells (iPS cells). To create these killer cells, the team first had to reprogram T lymphocytes specialized in killing a certain type of cancer, into iPS cells. The iPS cells then generated fully active, cancer-specific T lymphocytes. These lymphocytes regenerated from iPS cells could potentially serve as cancer therapy in the future.

The immune system and the process of T-cell differentiation
Pathogenic bacteria and viruses are sensed by antigen-presenting cells, such as dendritic cells, and the signal is transmitted to helper T (Th) cells. Th1 cells direct killer T cells to attack virus-infected cells and cancerous cells, while Th2 cells direct B cells to produce antibodies to attack pathogens. Most immune cells differentiate from hematopoietic stem cells in the bone marrow. T cells, however, differentiate in the thymus, where T-cell progenitor cells from the bone marrow differentiate into DP thymocytes, which further differentiate into either helper or killer T cells. CD4, CD8 and TCR, are expressed on the surfaces of DP thymocytes; CD8 disappears with differentiation into helper T cells and CD4 disappears with differentiation into killer T cells.
Credit: Riken

Previous research has shown that killer T lymphocytes produced in the lab using conventional methods are inefficient in killing cancer cells mainly because they have a very short life-span, which limits their use as treatment for cancer. To overcome these problems, the Japanese researchers led by Hiroshi Kawamoto and presenting their results in the journal Cell Stem Cell online today, reprogramed mature human killer T lymphocytes into iPS cells and investigated how these cells differentiate.

Video: Natural Killer Cells

The team induced killer T lymphocytes specific for a certain type of skin cancer to reprogram into iPS cells by exposing the lymphocytes to the 'Yamanaka factors'. The 'Yamanaka factors' is a group of compounds that induce cells to revert back to a non-specialized, pluripotent stage. The iPS cells obtained were then grown in the lab and induced to differentiate into killer T lymphocytes again. This new batch of T lymphocytes was shown to be specific for the same type of skin cancer as the original lymphocytes: they maintained the genetic reorganization enabling them to express the cancer-specific receptor on their surface. The new T lymphocytes were also shown to be active and to produce the anti-tumor compound interferon γ.

"We have succeeded in the expansion of antigen-specific T cells by making iPS cells and differentiating them back into functional T cells. The next step will be to test whether these T cells can selectively kill tumor cells but not other cells in the body. If they do, these cells might be directly injected into patients for therapy. This could be realized in the not-so-distant future." explains Dr Kawamoto.


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