Researchers at Columbia University Medical Center continue to make progress in developing effective viral-based therapies for cancer.

Two papers about promising research with genetically engineered viruses studied in mice, published in the journals Cancer Research and the Proceedings of the National Academy of Sciences ( PNAS ), bring us significantly closer to this objective and the start of clinical trials with these viral-based therapies in cancer patients.

Both papers were led by Paul B. Fisher, at Columbia University College of Physicians and Surgeons.

In the Cancer Research paper, the researchers discuss the development of a "terminator" virus, which was administered to mice with pancreatic cancers at both primary and distant sites.

When the virus was injected directly into the primary tumor, the virus destroyed not only the primary tumor, but also distant tumors. While the infection caused by the virus was sufficient to kill the primary tumor, a second weapon added to the virus Interferon-gamma ( IFN-gamma ) eliminated the metastases.
IFN-gamma elicited an anti-tumor immune response against the distant metastatic cancer cells.

In the PNAS paper, Fisher and the team describe the production of a virus conceptually similar to the "terminator" virus, which selectively replicates and kills breast cancer cells in mice.
Human breast tumor xenografts were established on both sides of immune-deficient mice.

Results found that treating the tumors on just one side of the animal with very few injections of this modified 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-gamma as the other virus did, this virus carried a gene called mda-7/IL-24, a novel gene identified and cloned in 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."

The "terminator" viruses have the potential to become effective treatments for a wide range of tumors - such as ovarian, pancreatic, breast, brain ( glioma ), prostate, skin ( melanoma ) and colon cancer - because the virus is constructed to exploit a characteristic of all solid cancers.

Source: Columbia University Medical Center, 2005


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