Columbia Scientists Develop Cancer Terminator Viruses

Bothpapers were led by Paul B. Fisher, M.Ph., Ph.D., professor of clinicalpathology and the Michael and Stella Chernow Urological Cancer ResearchScientist at Columbia University College of Physicians and Surgeons.

Inthe Cancer Research paper, the researchers discuss the development of a"terminator" virus, which was administered to mice with pancreaticcancers at both primary and distant sites (akin to metastases). Aspredicted, when the virus was injected directly into the primary tumor,the virus destroyed not only the primary tumor, but also distanttumors. While the infection caused by the virus was sufficient to killthe primary tumor, a second weapon added to the virus ¡Vinterferon-gamma (IFN-ƒ×) ¡V eliminated the metastases. IFN-ƒ× elicitedan anti-tumor immune response against the distant metastatic cancercells.

In the PNAS paper, Dr. Fisher and the team describe theproduction 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 ofimmune-deficient mice. Results found that treating the tumors on justone side of the animal with very few injections of this modified virusnot only cured the injected tumors, but also resulted in thedestruction of the tumors on the opposite side of the animal. Insteadof carrying IFN-ƒ× as the other virus did, this virus carried a genecalled mda-7/IL-24, a novel gene identified and cloned in Dr. Fisher'slaboratory, which is selectively toxic to cancer cells and is now inphase II clinical trials as a cancer gene therapeutic.

"We areextremely excited about these results and the prospect of one day usinga form of the cancer terminator virus in human clinical trials," saidDr. Fisher, the study's senior author. "While the results of thesetrials need to be investigated further and replicated in future trials,we believe that viral-based therapies will someday soon be a standardpart of the cancer armamentarium."

About the "Terminator" Viruses

The"terminator" viruses have the potential to become effective treatmentsfor a wide range of tumors - such as ovarian, pancreatic, breast, brain(glioma), prostate, skin (melanoma) and colon cancer - because thevirus is constructed to exploit a characteristic of all solid cancers.However, clinical trials are necessary before such treatments can beapproved by the U.S. Food and Drug Administration and available forpatients.

These publications are a continuation of researchpublished in the Jan. 25, 2005 issue of PNAS, where the same researchteam, also led by Dr. Fisher, incorporated gene therapy into aspecially designed non-replicating virus to overcome one of the majorhurdles of gene therapy: its tendency to kill normal cells in theprocess of eradicating cancer cells. The virus eradicated prostatecancer cells in the lab and in animals, while leaving normal cellsunscathed.

The present cancer "terminator" viruses represent thenext generation of therapeutic viruses that permit replication uniquelyin cancer cells with simultaneous production of immune modulating andtoxic genes. These viruses effectively eliminate primary tumors anddistant tumors (metastases) without harming normal cells or tissues.

Dr.Fisher's cancer research team includes Columbia University MedicalCenter investigators: Drs. Zao-zhong Su (research scientist), DevanandSarkar (associate research scientist), Nicolaq Vozhilla (pathologytechnician), Eun Sook Park (pathology technician) and Pankaj Gupta(associate research scientist). Two scientists from VirginiaCommonwealth University in Richmond, Va. are also involved in theresearch: Mr. Aaron Randolph (graduate student) and Dr. KristofferValerie (professor).