Cancer Terminator Viruses

Researchers are developing the next generation of effective viral-based therapies for cancer. Two recent studies using genetically modified viruses in mice bring investigators considerably closer to this goal and the start of clinical trials with these viral-based therapies in cancer patients.

One study was published in the September 19, 2005, issue of the journal Cancer Research and the other study was published in the September 20, 2005, issue of the journal Proceedings of the [U.S.] National Academy of Sciences. Both studies were lead by Paul B. Fisher, M.Ph., Ph.D., professor of clinical pathology at Columbia University College of Physicians and Surgeons (New York, NY, USA).

In the study published in Cancer Research, the scientists reported the development of a terminator virus, which was injected into mice with pancreatic tumors at both primary and distant sites (metastases). As expected, when the virus was injected directly into the primary tumor, the virus killed not only the primary tumor, but also the distant tumors. Whereas the infection caused by the virus was sufficient to destroy the primary tumor, a second substance added to the virus iV interferon-gamma (IFN-ƒ×) iV eliminated the metastases. IFN-ƒ× produced an anti-tumor immune response against the distant metastatic cancer cells.

In the study, Dr. Fisher and coworkers describe the production of a virus conceptually similar to the terminator virus, which selectively replicates and destroys breast cancer cells in mice. Human breast tumor xenografts were established on both sides of immune-deficient mice. Findings showed that treating the tumors on just one side of the animal with very few injections of this engineered virus not only cured the injected tumors, but also resulted in the destruction of the tumors on the opposite side of the animal. Instead of carrying IFN-ƒ× 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 Dr. 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 terminator viruses have the potential to become effective treatments for a wide range of tumors, such as pancreatic, ovarian, breast, brain (glioma), prostate, skin (melanoma), and colon cancer because the virus is modified to exploit a characteristic of all solid tumors. However, clinical trials are needed before such treatments can be approved by the U.S. Food and Drug Administration (FDA) and made available for patients.

These studies are a continuation of earlier research where the same team, also led by Dr. Fisher, integrated gene therapy into a specially designed non-replicating virus to overcome one of the key obstacles of gene therapy: its tendency to destroy healthy cells in the process of killing cancer cells. The virus eradicated prostate cancer cells in the lab and in animals, while leaving normal cells unharmed.

These cancer terminator viruses represent the next generation of therapeutic viruses that allow replication exclusively in cancer cells with simultaneous production of immune-modulating and toxic genes. These viruses have been shown in these studies to effectively eliminate primary tumors and distant tumors without harming healthy cells or tissues.