Researchers have successfully eliminated chemotherapy-resistant ovarian cancer cells in mice using a single injection of two viruses genetically combined and altered to be safe, leading to long-term survival and demonstrating a potential breakthrough treatment for women.
In a study published Thursday in Virology with funding from Women’s Health Research at Yale, the authors report that the treatment selectively targeted and killed ovarian cancer cells in the abdomen and in the brain and could activate the body’s immune system to provide long-term protection against tumor growth.
The paper was accepted for publication shortly before the death of the lead author, Dr. Anthony van den Pol, on Oct. 28, capping a four-decade career in which he achieved trailblazing advancements in neurobiology, virology, and oncology.
“The body does not recognize ovarian cancer as a foreign invader that would normally trigger the immune system to attack, so the cancer can continue to grow unimpeded,” Dr. van den Pol had said in an interview about the work in 2017. “But the reason these viruses can infect cancer cells, and particularly ovarian cancer cells, is that 80 percent of human tumors have a deficient innate immune response. The cancer cell cannot defend itself against a virus.”
In this new study, Dr. van den Pol used genetic elements of the Lassa virus (LASV) combined with an attenuated variant of vesicular stomatitis virus (VSV) to produce what is known as a new chimeric virus, which was rendered safe from any danger of infecting the body. He had already demonstrated in a mouse model that chimeric LASV-VSV could selectively infect a brain tumor called glioma and lead to long-term survival with no persisting trace of cancer.
After demonstrating that LASV-VSV infected and killed human ovarian cancer cells in laboratory cultures, the researchers injected the altered virus into mice with ovarian cancer. Mice receiving a single injection showed no tumor growth and no cancer recurrence for as long as they were monitored. In contrast, mice that received standard chemotherapy treatment for ovarian cancer — or no treatment at all — did not survive.
About one in every 78 women in the United States will develop ovarian cancer. It is the fifth most lethal cancer in women.
One of the reasons ovarian cancer can become deadly is that it can develop into late stages before showing symptoms, and it recurs in about 80 percent of patients who receive successful surgery and chemotherapy treatment. And when it comes back, it often invades deep into large portions of the abdomen and pelvis where it is hard to find and difficult to remove surgically. In addition, the cancer often mutates to develop a resistance to chemotherapy.
Ovarian cancer that spreads to the brain can be highly deadly. Dr. van den Pol’s team demonstrated that after an injection of LASV-VSV, mice with human ovarian cancer cells in their brains were tumor-free and showed long-term survival, compared with untreated mice that died within six days.
In addition, the researchers showed that mice first injected with ovarian cancer cells infected with LASV-VSV and then with non-infected ovarian cancer cells showed a rapid reduction in tumors and no tumor growth or spread over time. The authors note that this long-term outcome was likely due to the body’s immune response and not the continued presence of the virus, which would have been eliminated by the time the subjects were exposed to ovarian cancer cells that had not been inoculated with LASV-VSV.
Other authors on the study include Dr. Xue Zhang, E. Lima, Mary Pitruzello, Dr. Nazli Albayrak, and John Davis of Yale School of Medicine, and Dr. Gil Mor and Dr. Ayesha Alvero of Wayne State University School of Medicine. They noted that research indicates LASV-VSV has potential for safe and effective use in humans.
“Dr. van den Pol’s profound insights and scientific brilliance will be greatly missed,” said WHRY Director Carolyn M. Mazure, Ph.D. “But his legacy of achievements will continue to fuel our interventions and inspire our research.”