Can a Flu Shot Be Used to Improve Cancer Immunotherapies?

Flu Vaccine

Researchers with Rush University Medical Center injected tumors with flu vaccines, even some FDA-approved seasonal flu shots, and found that this attracted immune cells to attack the tumors. In the language of immuno-oncology, it turned cold tumors, which don’t cause much of an immune reaction, hot. The research was published in the Proceedings of the National Academy of Sciences.

“We wanted to understand how our strong immune responses against pathogens like influenza and their components could improve our much weaker immune response against some tumors,” said Andrew Zloza, assistant professor in Rush Medical College’s Department of Internal Medicine and senior author of the study.

Some immunotherapies against cancer leverage live pathogens, but they haven’t shown lasting effects in most patients or cancer types. Pulling data from a National Cancer Institute database, the research team found that lung cancer patients who had been hospitalized for a lung infection caused by influenza at the same time lived longer than lung cancer patients who had no flu. They ran experiments and found similar results in mice with tumors and flu lung infections.

“However, there are many factors we do not understand about live infections, and this effect does not repeat in tumors where influenza infections do not naturally occur, like skin,” Zloza said.

So they worked with an inactivated flu virus, which is basically a flu vaccine. A direct injection of this vaccine into the skin melanoma of the mice caused the tumors to either shrink or grow slower. It appears to increase the proportion of dendritic cells in the tumor, which are immune-stimulating cells. This resulted in an increase in CD8+ T-cells, which recognize and kill cancer cells.

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In addition, injecting the vaccine into the skin melanoma tumor on one side of the body also reduced growth of a second skin tumor on the other side of the mouse’s body that had not been injected. This means that the “vaccine,” although dosed locally, had a systemic effect.

The researchers also observed similar systemic results in a mouse model of metastatic triple-negative breast cancer where it reduced the primary tumor but also the metastasis of the breast tumor to the lungs.

“Based on this result,” Zloza said, “we hope that in patients, injecting one tumor with an influenza vaccine will lead to immune responses in their other tumors as well. Our successes with a flu vaccine that we created made us wonder if seasonal flu vaccines that are already FDA-approved could be repurposed as treatments for cancer.”

He went on to add, “Since these have been used in millions of people and have already been shown to be safe, we thought using flu shots to treat cancer could be brought to patients quickly.”

And their experiments showed that they did. Additional experiments involved a mouse model called AIR-PDX, where they implanted tumor cells and immune cells from a cancer patient into a mouse that didn’t have a functioning immune system of its own. This prevents the mouse from rejecting the implanted cells. They used a human lung tumor and a melanoma metastasis in their AIR-PDX models. What they found was that injecting the flu shot into the patient-derived tumors also caused them to shrink, while the untreated tumors continued to grow.

They also ran experiments using checkpoint inhibitors, a type of immuno-oncology treatment, such as Merck’s Keytruda (pembrolizumab). The flu vaccines reduced cancer growth alone whether the tumor was responsive to checkpoint inhibitors or not. And when they combined the flu vaccine with a checkpoint inhibitor, they showed an even greater decrease in tumor growth.

“These results propose that eventually both patients who respond and who do not respond to other immunotherapies might benefit from the injection of influenza vaccines into the tumor, and it may increase the small proportion of patients that are now long-term responders to immunotherapies,” Zloza said.

The researchers used five different flu shots from the 2017-2018 flu season in their research, and four were effective in fighting tumors.

The next step is to plan clinical trials. Because the flu vaccine is already FDA approved, the study time may be shorter.

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