Early Trial Shows 'Smart Bomb' Virus Extends Survival in Patients With Glioblastoma

The median survival of a patient with glioblastoma, the most aggressive form of brain cancer, is 15 to 18 months, according to the National Cancer Institute.

With no cure for the deadly disease, researchers fiercely continue to investigate new ways to improve survival rates, which can be less or more than the estimated median survival depending on molecular markers in each patient.

Findings from an early phase clinical trial that used a so-called “smart bomb” virus — which was altered to attack tumor cells rather than normal cells — appeared to show promise in this area.

“Oncolytic viruses are a potential new treatment that is completely different from the standard chemotherapy and radiation, and we think the side effects of this treatment could be less,” Frederick Lang, M.D., FACS, FAANS, professor and director of clinical research in the Department of Neurosurgery at MD Anderson Cancer Center in Houston, said in an interview with CURE.

In the phase 1 study, researchers used the virus, DNX-2401, to attack the cancer cells in 25 patients whose glioblastoma had recurred after surgery and other prior treatment. Through a small procedure, the engineered virus was injected one time directly into the tumors. “Patients can usually go home the next day,” Lang said.

Five patients lived for three years or longer, and three of them had durable complete responses, meaning all signs of cancer disappeared in response to treatment. Despite this response, the three patients suffered recurrences just short of the five-year mark that proved to be deadly.

In addition, the researchers saw tumor reduction in 18 patients and a median overall survival of 9.5 months. Through analyzing the tissue after treatment, the researchers discovered that the virus works in two ways.

“The first is the virus infects tumor cells and directly kills them,” Lang said. “The second way is that the tumor is immunosuppressive, meaning the immune system can’t get into the brain tumor very well. A virus is very immunogenic. In other words, your immune system knows to go in and attack the virus because it wants to get rid of it,” explained Lang.

“We hypothesized that because the virus is killing the cells and releasing tumor proteins the immune system now starts to think that the tumor is a virus. It sees all the tumor proteins and it thinks they are foreign, so it starts attacking the tumor. If that can happen then the immune system takes out the whole tumor,” he added.

Although the trial showed extended survival in 20 percent of patients, 80 percent did not have a strong response to treatment, which Lang said could be because of the way treatment was delivered. “We used our hands to inject the virus and we think it’s not a good technique because the virus comes out when you do it that way,” he said. “So, we worked with a company to develop a refined cannula (a thin tube inserted into a vein or body cavity) that prevents the backflow. Now we hook the whole thing up to an infusion pump and infuse it slowly.”

Researchers are most excited that the treatment can be delivered with minimal toxicities. “Since the virus isn’t given to the whole body (it’s just in the tumor), it had minimal side effects,” Lang said. “Sometimes the person had a slight fever, but that was relatively rare. We couldn’t find the virus in blood or urine, so it wasn’t getting systemically through the body. There was no nausea, vomiting or hair loss that you get with radiation or chemotherapy.”

The next steps, according to Lang, focus on who this works best for and how to best manipulate the immune system. One way in which this is being studied is through animal models where the virus is being tested in combination with Keytruda (pembrolizumab), an immunotherapy that works to block the protein programmed cell death 1, more commonly known as PD-1, and helps the immune system kill cancer cells.

The researchers also hope to gain approval from the Food and Drug Administration to begin a clinical trial that would deliver the virus by using stem cells. The stems cells would be injected into the blood and then they would hone to the tumor and release the virus, Lang noted.

“None of this can happen without patients volunteering,” Lang said. “Going on clinical trials is critical. We are always grateful for people who are willing to do some of these experimental therapies.”