Herpes Virus Can Kill TNBC

In lab studies at the Memorial Sloan-Kettering Cancer Center, the mutant herpes virus NB1066 was effective in killing triple-negative breast cancer cells, according to research reported at the American College of Surgeons 97th Annual Clinical Congress. The bonus: The virus kills cancer cells while not destroying healthy ones, a huge improvement over current forms of chemotherapy.

In the research on TNBC cells, 90 percent of the most sensitive cells were killed within a week of treatment; 70 percent of the least sensitive cells were killed. In research on mice, the tumors had largely disappeared within 20 days.

The release, from the American College of Surgeons:

SAN FRANCISCO—Researchers from Memorial Sloan-Kettering Cancer Center in New York City report they have successfully treated triple-negative breast cancer (TNBC) in petri dishes and in mouse models with a method based upon a herpes simplex virus. The study on the viral-based therapy was reported today at the 2011 Annual Clinical Congress of the American College of Surgeons.

Triple-negative breast cancer is an aggressive type of breast cancer that can account for up to 20 percent of all cases and is responsible for a disproportionate number of breast cancer deaths, according to the researchers. Moreover, the disease is most likely to surface in younger women (< 35 years old), especially if they are African American or Hispanic. Because these types of cancerous tumors do not express the estrogen receptor, progesterone receptor, or HER-2 receptor, found in other more common types, newer targeted therapies such as tamoxifen and Herceptin are ineffective against the disease.

“Triple-negative breast cancer patients are in dire need of targeted therapies,” according to Sepideh Gholami, MD, a research fellow in the laboratory of Yuman Fong, MD, FACS, at Memorial Sloan-Kettering Cancer Center. “Although these tumors respond to a variety of chemotherapies, they have a high recurrence and metastatic rate.”

In the study, Dr. Gholami and her colleagues examined TNBC cell lines and infected them with a herpes simplex virus called NV1066. After treatment with the virus, more than 90 percent cell kill was achieved in all cell lines within a week. Furthermore, the researchers injected TNBC cells into laboratory mice. After treating the mouse models with the virus, and measuring the change in the tumors over 20 days, they found that the tumors had largely disappeared.

It was very surprising to see such an intense response. “The difference was dramatic, because sometimes we can stop tumor growth, but not necessarily achieve tumor regression,” Dr. Gholami said. “Our results are very exciting because we may be coming up with an approach that could potentially exploit the unique vulnerabilities of these specific cancer cells.”

Moreover, Dr. Gholami explained that TNBC cells have high levels of p-MAPK, a protein that promotes cancer cells to grow and has been reported as a potential cause for resistance to current conventional therapies. Knowing that the herpes virus specifically targets cells that over express this protein is the reason she chose to test this treatment protocol. “When we infect TNBC cells with the herpes virus and measure p-MAPK levels, the protein level decreases with time after treatment with the virus,” Dr. Gholami said.

The hope is that advances in oncolytic viral therapy, which uses viruses tailored to target and destroy cancer cells while sparing healthy cells, will allow researchers to develop more effective strategies for hard-to-treat cancers. A similar herpes virus has been tested in clinical trials against head and neck cancers. But this is the first laboratory study to show promise in using the therapy to treat TNBC.

The next steps, Dr. Gholami said, are to map out the pathways in which the virus kills the tumor cells to determine how to improve upon this mechanism. In the future, the Fong laboratory, which is on the forefront in oncolytic viral therapy research, will continue this avenue of investigation in animal studies. The team will also work to identify leads to understand what existing chemotherapy drugs can be used synergistically with this viral therapy. Finding complementary treatments that kill fast-growing cancer cells and combat resistance is the key to possibly making a cure a reality.

If additional animal studies are also positive, human clinical trials could be on the horizon. “Our goal is to improve this version of the virus and get it into a clinical trial,” Dr. Gholami said. “Ultimately, I believe the treatment for TNBC will be a multimodality targeted treatment approach: potentially using a viral-based therapy plus some other targeted chemotherapy or radiation.”

The study was supported by grants from the National Institutes of Health and the Flight Attendant Medical Research Institution.

Other participants in the study include Chun-Hao Chen, MD; Sizhi Paul Gao, MD, PhD; Joshua Carson, MD, PhD; Taejin Song, MD, PhD, FACS; Jackie Bromberg, MD, PhD; and Yuman Fong, MD, FACS.