By Benjamin Ross
January 22, 2020 | Researchers from Rush University Medical Center are taking a unique approach to cancer immunotherapy: a flu shot. In a recent study published in PNAS (DOI: 10.1073/pnas.1904022116), the physicians and scientists detail how injecting the influenza vaccine directly into a tumor can either shrink or slow the growth of it.
Andrew Zloza, assistant professor in Rush’s Department of Internal Medicine in the Division of Hematology, Oncology, and Cell Therapy, and senior author of the study, tells Diagnostics World News this technique is easily translatable to the clinic, and can be a repurposed use for the flu shot that can have a benefit for cancer patients.
Zloza and his colleagues began their research by looking at the body’s immune system, specifically the immune response to infections.
“Infections are common; we’re always infected with things,” says Zloza. “Sometimes we know we are because we feel sick, and sometimes our immune system gets to the infection before we can even tell we’re infected.”
But why is the immune system mostly unable to defend against cancer?
“The majority of patients’ tumors are what we consider ‘cold,’” Zloza says, “which means either there aren’t a lot of immune cells there to fight against the tumor, or that the immune cells that are there are the kind that suppress the immune response instead of activating it.”
Essentially, whenever we have an immune response, we need cells to start the response and kill off the infection, then we need cells to suppress the response because the infection’s gone.
“And what happens is that in cancer the cells that are around the tumor are mostly suppressive cells,” says Zloza. “This is one reason why the tumor is not controlled by the immune system, and sometimes it’s also the reason patients don’t respond to their cancer therapy, especially immunotherapy.”
From previous research, Zloza and his colleagues learned that when there’s an infection somewhere, the immune system directs a lot of its resources to that area without knowing what type of infection its supposed to be fighting. This means that when cells designed to battle an infection like influenza show up, cells against tumors show up as well.
“So we thought if we put an infection in the same place as a tumor, we should see something good happen,” Zloza says.
Using a mouse model, Zloza and his team grew a tumor in the lungs and put the influenza infection in the lungs as well. Results showed that having influenza as well as a tumor in the same location resulted in a smaller tumor. “It was a positive effect of having influenza in the lungs when there’s a tumor there as well,” says Zloza.
The next step was to see if there was a similar response for humans, Zloza says. For this phase of the study, the researchers turned to the SEER-Medicare database, where they were able to find over 30,000 patients with lung cancer that were followed for 100 months or more.
“We took those patients and separated them into two groups: a group of patients that had also been hospitalized for influenza during those 100 months, and a group that had never been hospitalized for influenza,” Zloza says. “What we saw there was that the patients who had one or more hospitalizations for influenza during the course of their lung cancer had a better survival rate.”
Excited by these observations, Zloza says the study’s authors wanted to see if the same principle could be applied to other sites in the body. They settled on melanoma and injected the influenza virus in the same location as the skin cancer. But they didn’t see the same results as they did with lung cancer because influenza never produced an infection on the skin. “[The immune system] can’t respond to the influenza if the influenza doesn’t produce an infection,” Zloza says.
The team realized they could trigger a response from the immune system by heat-inactivating the influenza, causing it to break down into its main components, which increases the proportion of immune-stimulating cells. “Then there’s no requirement for infection if we take those components, inject them into the tumor, and the immune system recognizes those components,” says Zloza. “So that’s what we did, we heat-inactivated the influenza, injected it into the melanoma, and we saw a reduction in tumor growth.”
Zloza recalls a moment when they were having a meeting and he had a moment of “eureka.”
“I said, ‘That sounds like the flu shot. Why don’t we just buy the flu shot and try that?’” he says. “So we did. We took several versions of the flu shot that were available that season that were FDA-approved for patients, and we injected them into the tumors of the mice. We saw that it all still worked.”
Zloza says the beauty of the flu shot is that it’s relatively cheap and an already proven treatment, having been approved by the FDA to treat millions of people. The core component of the flu shot also means its effectiveness is unlikely to change through the different versions of the vaccine.
Currently, Zloza and his colleagues are actively writing protocols for setting up clinical trials, hoping within the next couple of months to have several trials up and running.
In retrospect, Zloza says he’s surprised no one’s thought of this approach before. “When I tell people we just showed we can use the flu shot to treat cancer, they’re usually surprised that it works. And when I tell them how it works, they then say, ‘Nobody’s tried that before?’” he laughs.