Marisa Peryer, Senior Photographer

A new Yale study showed that certain genetically modified viruses can cure ovarian cancer in mice. It may be of use in the treatment of ovarian cancer in humans.

Researchers at the Yale School of Medicine have tested a chimeric virus — containing genes from two different viruses — that can selectively infect and kill ovarian cancer cells in mice. Their findings represent a potential breakthrough in the long-term treatment of ovarian cancer in humans. The study was published in the journal Virology on Nov. 12, two weeks after the death of the paper’s lead author Anthony Van den Pol, former professor of neurosurgery and psychiatry at Yale.

“Every year, around 20,000 women are diagnosed with ovarian cancer, which is a smaller number compared to cancer types such as breast cancer,” said Gil Mor, the scientific director of the C.S. Mott Center for Human Growth and Development at Wayne State University and a co-author of the paper. “However, unfortunately only around 4,000 of those women can survive the disease.”

The main reason behind the lethality of ovarian cancer is the lack of treatments preventing the recurrence of the disease. In 80 percent of cases, patients who respond positively to chemotherapy still experience a return of the disease, according to Mor. He explained that once the cancer comes back and begins to spread, there is little that doctors can do.

The inspiration for the study was born out of a collaboration between Van den Pol and Mor many years ago, when they worked in adjacent labs at the Yale School of Medicine. Van den Pol, a research scientist in the Neurosurgery Department, had concentrated his research on the long-term treatment of brain tumors. Mor, on the other hand, had been working on treatments for ovarian cancer. The two scientists decided to collaborate to find an alternative treatment for ovarian cancer through oncolytic viruses, which selectively infect and kill cancer cells.

In the experiment’s in vitro phase, in which the research takes place in laboratory tubes or petri dishes without a living component, researchers made a virus called Lassa-VSV in the laboratory. Lassa-VSV consists of three parts: the Lassa virus, the vesicular stomatitis virus, or VSV, and a fluorescent label to facilitate tracing, according to Nazli Albayrak, a scientist who was involved in the in vitro phase. During this phase, the team infected different ovarian cancer cell lines, eventually choosing the ones that were infected most frequently to proceed with the research. 

Then, after deciding on the cell line, the team injected tumor cells into the bodies of the mice, the paper explains. As the tumor cells began to replicate, the team then injected the Lassa-VSV virus into the tumor clusters. They observed that the virus infected the tumor cells very effectively yet did not harm the healthy cells that were present in other parts of the mice.

In gynecologic oncology, patients who are suffering from ovarian cancer are currently provided with chemotherapeutic agents after their surgeries. However, as Mor and Albayrak also mentioned, chemotherapeutic agents are not a cure for these patients.

This observation prompted the researchers to compare the effectiveness of chemotherapeutic agents and the Lassa-VSV chimeric virus in clearing tumor cells from the mice’s bodies. They found that the virus was able to get rid of more cancer cells than the chemotherapy treatment and do so without harming healthy mouse cells. Albayrak also noted that the mice treated with the Lassa-VSV virus lived approximately four times longer than those treated with chemotherapeutic agents.

Vaagn Andikyan, assistant professor at the School of Medicine who also works in gynecologic oncology, said that this form of treatment could be more effective in treating cancer in humans and be a prevalent option in the future.

“It is a very intriguing, very unique approach to ovarian cancer, and this approach may be applicable for several other malignancies,” Andikyan said.

Andikyan works with the standard treatment of ovarian cancer, a field that is rapidly changing through new drugs and new treatment procedures. He said that this paper’s approach to treating ovarian cancer is promising to him.

According to Mor, if the clinical phases — in which human subjects are involved — prove to be successful, many people can benefit greatly from the researchers’ discovery. This approach may even lead to the discovery of a vaccine against tumors and even in different cancer types, Andikyan said.

Van den Pol died on Oct. 28, the day on which the team’s paper was accepted to Virology, a pioneer journal in the field. Mor said that the team would miss Van den Pol and continue to honor him in their future research. Albayrak and Mor noted that they did not know Van den Pol had a condition until receiving news of his death.

“He was a very private person, and we knew that he did not feel well, but we never realized the magnitude of his disease,”  Mor said.

The team and Van den Pol’s colleagues at the Yale School of Medicinewere saddened by the news, yet the team is hopeful about the discovery they recently made and will continue to include Van der Pol as an author in their future studies.

Ovarian cancer is the fifth-most deadly cancer among women, according to the American Cancer Society.

Elifnaz Onder | elifnaz.onder@yale.edu