Scientists' terminator' virus destroys tumour growth
effective viral-based therapies for cancer in which 'terminator'
viruses are deployed to destroy primary tumours.
The "terminator" viruses have the potential to become effective treatments for a wide range of tumours, such as ovarian, pancreatic, breast, brain (glioma), prostate, skin (melanoma) and colon cancer.
The researchers, from the Columbia University Medical Centre, have hailed these "terminator" viruses as the next generation of therapeutic viruses that allow replication uniquely in cancer cells. At the same time, immune modulating and toxic genes are produced.
These viruses effectively eliminate primary tumours and distant tumours (metastases) without harming normal cells or tissues.
This is its main advantage. Current day cancer treatments suffer from debilitating side effects caused by toxic compounds that attack healthy cells, which can limit treatment to sub-optimal levels.
In the first of two studies, published in Cancer Research, the researchers administer the virus to mice with pancreatic cancers at both primary and distant sites (akin to metastases).
When the virus was injected directly into the primary tumour, the virus destroyed not only the primary tumour, but also distant tumours. While the infection caused by the virus was sufficient to kill the primary tumour, a second weapon added to the virus interferon-gamma (IFN-ƒx) eliminated the metastases. IFN-ƒx elicited an anti-tumour immune response against the distant metastatic cancer cells.
The second paper, published in PNAS, Paul Fisher and the team describe the production of a virus similar to the "terminator" virus, which selectively replicates and kills breast cancer cells in mice.
Human breast tumour xenografts were established on both sides of immune-deficient mice. Results found that treating the tumours on just one side of the animal with very few injections of this modified virus not only cured the injected tumours, but also resulted in the destruction of the tumours on the opposite side of the animal.
Instead of carrying IFN-ƒx as the other virus did, this virus carried a gene called mda-7/IL-24, a novel gene identified and cloned in Dr. Fisher's laboratory, which is selectively toxic to cancer cells and is now in phase II clinical trials as a cancer gene therapeutic.
"We are extremely excited about these results and the prospect of one day using a form of the cancer terminator virus in human clinical trials," said Fisher, the study's senior author.
"While the results of these trials need to be investigated further and replicated in future trials, we believe that viral-based therapies will someday soon be a standard part of the cancer armamentarium."
These publications are a continuation of research published in the Jan. 25, 2005 issue of PNAS, where the same research team, also led by Fisher.
Here the research incorporated gene therapy into a specially designed non-replicating virus to overcome one of the major hurdles of gene therapy: its tendency to kill normal cells in the process of eradicating cancer cells.
The virus eradicated prostate cancer cells in the lab and in animals, while leaving normal cells unscathed.
The research is a variation on a current theme occurring in drug R&D, which concentrates on using viruses as a drug delivery system.
The virus is intentionally used as a method of attachment allowing researchers to not only target particular cells, but also to gain entry more easily into the cells.
Once it reached the tumour, the viral transporter transfers a gene to both the subject and tumour cells that then infected the cells.
