Technique to Induce Cancer Cells to ‘Commit Suicide’

Developed by Hebrew University Scientists

A new technique for tricking cancer cells into “committing suicide” and thus preventing their spread has been developed by researchers at the Hebrew University of Jerusalem. Their work is described in the September issue of Nature Biotechnology, which was published this week in its Internet version.

The technique involves the engineering of a virus that will induce the cancer cell to behave in a manner similar to that of normal cells that are under attack.

In normal cells which have been attacked by a virus, a protein known as PKR is activated as the result of RNA replication within the affected cell. This protein causes the cell to destroy itself, thus preventing the spread of the virus. Normally, PKR stays dormant, doing nothing unless the cell is provoked by an invading virus.

Graduate student Alexei Shir (who has since earned his Ph.D.), together with his advisor, Alexander Levitzki, who is Wolfson Family Professor of Biochemistry at the Alexander Silberman Institute of Life Sciences at the Hebrew University, devised a strategy designed to “trick” cancer cells into activating PKR without activating it in normal cells. Shir and Levitzki developed a technique which involves the engineering of a unique virus, from the same family as the HIV virus, which can be “smuggled” into the cancer cells. This virus, in turn, triggers the PKR activation in the cancerous cells – which otherwise would not occur – and induces them to die, much as ordinary cells would when attacked by a virus.

The virus developed by the Hebrew University researchers is directed specifically against an especially virulent brain tumor cancer and is not harmful to normal cells. This represents a significant improvement over current chemotherapy treatments, which kill cancer cells but also have harmful effects on normal cells. In laboratory tests, the induced virus technique resulted in significant halting of the spread of the brain tumor. For his work, Dr. Shir was awarded one of the Kaye Innovation Awards at the Hebrew University earlier this year.

Prof. Levitzki said that other graduate students of his are now adapting this strategy to lymphoma and leukemia.

A start-up company, Algen Biopharmaceuticals, has been established by the Yissum Research Development Co. of the Hebrew University, together with Prof. Levitzki and investors, to further develop this technology. Prof. Levitzki cautioned that a great deal of laboratory and clinical work remains to be done before this technique will be able to be implemented in treatment of cancer patients.