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Vaccinating Against Melanoma: New NIH Grant Advances Cancer Vaccine Work at OU

Monday, October 31, 2016 - Campus News -

A new $562,825 million federal grant advances research aimed at making vaccines against melanoma a reality for more patients. The work also may help bring clinical trials of those new vaccines to Oklahoma.

Most of us are familiar with vaccines used to keep us from getting sick from diseases like tetanus, whooping cough, meningitis and more. They work by triggering the body’s immune system to recognize the disease and mount a strong immune response to prevent infection.

With cancers like melanoma, the vaccines are personalized for each patient based upon specific mutations unique to his or her tumor cells.

“With melanoma, everybody’s cancer is distinct. So it’s difficult to treat that with a drug or therapy that’s meant to work on everybody,” said William Hildebrand, PhD, professor of microbiology and immunology with the University of Oklahoma College of Medicine and member of the Stephenson Cancer Center.

So instead of looking for a single treatment for all patients, researchers focused their efforts on developing the single best immunotherapy for each patient.

“So the questions we are hoping to answer now include: how personalized will cancer therapies become; how effective will those personalized therapies be; and how practical will those therapies be? We are just beginning to explore those borders,” Hildebrand said.

Hildebrand and his team at the OU Health Sciences Center have been involved in the melanoma vaccine research work almost from the start.

“The beauty of your immune system is it has tremendous specificity. You can train it to only recognize and target melanoma cells, while leaving healthy cells in your body alone,” Hildebrand explained.

Colleagues in St. Louis first utilized genomics to find genes that were mutated in each patient’s melanoma cells but not in healthy cells. They uncovered thousands of mutations. Determining which of those mutations would be the best targets for vaccine development fell to the OU team.

Utilizing specific tests and computer algorithms, Hildebrand and fellow researchers predicted and then tested the handful of mutations that would be the best vaccine targets. With that information, colleagues in St. Louis developed personalized vaccines, essentially teaching the body’s own internal warriors to seek out and destroy melanoma cells. Early results were promising -- so promising that researchers applied for a new grant from the National Institutes of Health. This time, the goal is to take their early approach to developing personalized melanoma vaccines and make it even better.

“Right now, we’re using a little bit more of a circuitous route. It’s a little slower. It works. We can treat patients, but we can’t treat a large number of patients very quickly. So we’ve received funding to begin making this system more robust, more efficient and more sensitive,” Hildebrand said.

The grant application received a perfect score. It is news the team shares with pride. They also are excited about expanding their collaboration with colleagues, who recently moved their work from St. Louis to Johns Hopkins University in Baltimore, Maryland.

“Our first goal was to show that the approach works, and I believe we did that a year ago,” Hildebrand said. “Next, we hope to show that it is practical and that we can apply this approach to a large number of people with melanoma by making the process more efficient. Finally, we hope to be able to transfer this approach to other centers. We can bring what the physicians at Johns Hopkins are doing with patients here to Oklahoma. And they can take our approach for target identification and migrate it there.”

Expanding clinical trials of the melanoma vaccine work will take support and it will take funding. Hildebrand said the new NIH grant helps in that regard, especially when combined with local and regional support of clinical trials at the Stephenson Cancer Center.

“So there are a number of resources that are coming to bear when people begin to realize that you can treat cancers in a personalized way and thereby try to mitigate the side effects of treatment by directing the immune response specifically to the tumor,” Hildebrand added. “People would really like to harness that power, but you have to show them it’s practical, it’s robust and it’s reasonable. That’s our focus now.”

Because lung cancer, like melanoma, is unique to each patient, Hildebrand said the same personalized vaccine approach may eventually prove best for that disease as well.

Hildebrand's melanoma research is supported by grant R01CA204261 from the National Institutes of Health.

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