Science Daily — Herpes viruses, though not life-threatening, are usually considered to be embarrassing and annoying. Researchers at the LSU School of Veterinary Medicine, however, are using the virus to potentially fight breast cancer, which, according to the American Cancer Society, is the most common cancer among women.

Sections of breast cancers growing after implantation in mice were prepared for pathological examination. Panel A shows a breast cancer from a mouse that received the killed virus injection (control). Panel B shows a breast cancer from a mouse that received a liquid that was used to dilute the virus (control). Panel C shows a breast cancer from a mouse that received the live cancer fighting herpes virus. In panel C, it can be seen that breast cancer cells have been killed (Necrotic N) compared to panels A and B in which cancer cells are viable. (Credit: Image courtesy of Louisiana State University)

In fact, excluding cancers of the skin, breast cancer accounts for nearly one in three cancers diagnosed in U.S. women.

“Our immune systems are engineered to fight cancer,” said Dr. Konstantin “Gus” Kousoulas, professor of virology in the Department of Pathobiological Sciences and director of the Division of Biotechnology & Molecular Medicine.  “The human body’s T-cells belong to a group of white blood cells and play a central role in immunity.  However, cancer cells cause the T-cells to essentially fall asleep. 

“The tumor emits signals to down-regulate the T-cells. Our herpes virus can be engineered to awaken those cells and modulate the immune system so that it recognizes the tumor cells and destroys them.”

The herpes virus was engineered to selectively replicate in cancer cells; it does not affect normal cells. 

“Herpes virus replicate cells on their own,” said Kousoulas. “Cold sores are caused when the herpes virus replicates and kills normal cells; the cold sore is made up of the dead cells. Our herpes virus has been engineered to only replicate and destroy cancer cells, thus killing the tumor. Patients would not contract the herpes virus itself.”

The next step is to show that LSU’s virus can enhance the immune system. Besides destroying cancer cells, this herpes virus also has the potential to work as a vaccine. 

“The herpes virus is oncolytic, which means it kills the tumor, but we want to see now if it can be engineered to boost the immune system and prevent it from metastasizing,” said Kousoulas.

Kousoulas is collaborating with Dr. Augusto Ochoa, a world-renowned authority on cancer immunology and interim director of the Stanley S. Scott Cancer Center, which is part of the LSU Health Sciences Center in New Orleans, Louisiana. The two are working on the next phase of the study with support from the Louisiana Cancer Consortium. 

A German company, MediGene, has a similar herpes virus, which is in Phase 3 clinical trials for liver cancer. 

“MediGene has seen significant results,” said Kousoulas, “and their trial should be completed within six months.”

Kousoulas, however, believes that LSU’s virus has been improved to go beyond the capabilities of MediGene’s virus. 

“Our virus has been engineered to spread even better among cancer cells,” he said.  “It causes the cancer cells to fuse together so that the virus can then destroy the cells more efficiently. The virus can be used as a vector to express other genes. We can insert multiple genes into it to enhance its tumor-killing capabilities.”

Kousoulas recently discussed this exciting new research at the 4th International Workshop on Nanosciences and Nanotechnologies at Aristotle University in Thessaloniki, Greece. Part of the study has also been published in the May 2007 issue of Human Gene Therapy (Israyelyan, et al).

“History shows us that cancer cannot be treated using pharmaceuticals alone,” said Kousoulas.  “We have to look at new and innovative gene therapies if we are to move forward.”

The study is in the pre-clinical experiment phase right now.  Qyntessa Biologics, part of the Louisiana Emerging Technologies Center on the LSU campus in Baton Rouge, Louisiana, is preparing to produce these viruses under strict Food & Drug Administration guidelines called Good Manufacturing Practices, or GMP. 

The LSU School of Veterinary Medicine and the Stanley S. Scott Cancer Center will work with Qyntessa to get the virus to Phase 1 human experiments, for initial toxicological evaluation.  Phase 2 experiments expand the testing to a handful of patients, and Phase 3 testing uses 100 to 200 patients.  It will take at least three years to get to the Phase 3 testing stage.  Financial support for these studies has been obtained from the National Institutes of Health, The Louisiana Board of Regents Biotechnology Initiative, the Louisiana Cancer Consortium, and the Louisiana Gene Therapy Program of the LSU Health Sciences Center in New Orleans.

Note: This story has been adapted from material provided by Louisiana State University.

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