The research could lead to a new class of cancer therapies that selectively kill cancer cells.
"These engineered viruses kill cancer cells through a mechanism that is completely different from chemotherapy or radiation," said Dr. William Wold, chair of the department of molecular microbiology and immunology at Saint Louis University School of Medicine. "These viruses have the potential to treat many cancers that are resistant to currently available therapeutics. It also may be possible to use these viruses in combination with other therapies to create novel treatment regimens."
Dr. Wold and his colleagues Karoly Toth, Konstantin Doronin, Ann E. Tollefson, Mohan Kuppuswamy, Baoling Ying, Jacqueline Spencer, and Maria Thomas have been researching for many years ways to convert the relatively benign "adenovirus" that causes symptoms similar to the common cold in children into an anti-cancer drug that attacks and destroys cancerous cells.
Wold's group has developed several new "adenovirus cancer gene therapy vectors," changing these genes so the virus will attack cancer cells.
"Some of our vectors are designed to destroy many different types of cancers, others are designed to be specific to colon or lung cancer. In preclinical testing these vectors were highly effective against cancerous tumors and did not harm normal tissues."
The new research reported today in Cancer Research involves INGN 007 (VRX-007) and INGN 009 (VRX-009), two novel "oncolytic adenoviruses" that have been engineered to kill cancer cells via viral replication. These viruses can be engineered so that they are active in specific types of cancer cells. The data published today indicate that both efficiently killed cancer cells in culture. Specifically:
- INGN 009, which has been designed to kill cells that carry a mutation common in many colon cancers, efficiently killed cultured colon cancer cells, but not lung cancer cells.
- INGN 007 effectively killed both types of cancer cells. In an animal model of colon cancer, injection of either INGN 007 or INGN 009 into tumors suppressed tumor growth more efficiently than a negative control (five-fold and ten-fold suppression, respectively).
- INGN 007 also completely suppressed tumor growth in a lung cancer model of disease.
Louis Zumstein, Ph.D., director of research at Introgen Therapeutics Inc., which has licensed rights to these oncolytic viruses and other related technologies, said: "These preclinical data are very promising, and support our belief that oncolytic adenoviruses have enormous potential as a new class of cancer therapies that may provide potent and selective killing of cancer cells. These data also illustrate the flexibility of engineered oncolytic adenoviruses to target selected tumor types with great specificity."
A U.S. patent (No. 6,627,190) for this technology was awarded last year to Dr. Wold and his team of researchers. Introgen and VirRx, a biotechnology company founded by Wold and with a primary interest in cancer gene therapy, are collaborating on new therapies for cancer and other diseases. Introgen is a leading developer of biopharmaceutical products that use non-integrating genes to produce a therapeutic protein to treat cancer and other diseases. Introgen maintains integrated research, development, manufacturing, clinical and regulatory departments and operates a commercial- scale, CGMP manufacturing facility.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first M.D. degree west of the Mississippi River. Saint Louis University School of Medicine is a pioneer in geriatric medicine, organ transplantation, chronic disease prevention, cardiovascular disease, neurosciences and vaccine research, among others. The School of Medicine trains physicians and biomedical scientists, conducts medical research, and provides health services on a local, national and international level.