Vaccine injection

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BOSTON, Mass. — For most diseases, vaccinations tend to be a one-size-fits-all proposition. For patients dealing with the deadliest form of skin cancer however, scientists are taking a personalized approach to inoculations. Researchers in Massachusetts say that four years after melanoma patients received a personalized cancer vaccine, the immune response triggered by the shot “remains robust and effective” in keeping tumors under control.

The team from Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and the Broad Institute of MIT and Harvard say their findings show the “staying power” of the immune response generated by their vaccine, NeoVax.

The drug works by targeting specific proteins on each patient’s tumor cells. Researchers discovered that, nearly four years after vaccination, each patient’s immune system cells were not only active against distinctive proteins in the skin cancer cells, but also spread to other proteins in those tumors.

According to the American Cancer Society, melanoma makes up just one percent of skin cancers, but causes a majority of skin cancer deaths.

“These findings demonstrate that a personal neoantigen vaccine can stimulate a durable immune response in patients with melanoma,” says study co-leader Professor Catherine Wu in a media release. “We found evidence that the initial, targeted immune response has broadened over the years to provide patients with continued protection from the disease.”

How does the personalized skin cancer vaccine work?

The study involved eight patients who had undergone surgery for advanced melanoma, but were still considered at high risk of recurrence.

In a clinical trial, the group received NeoVax around 18 weeks after surgery. The vaccine is made from bits of proteins (epitopes) poking out from the cell surface to signal the immune system. Prof. Wu says that the epitopes in NeoVax come from neoantigens, which are abnormal proteins on tumor cells. They warn the body that a cell is cancerous and should be destroyed. Since neoantigens are found only on tumor cells, they trigger immune responses which spare normal cells from attack.

Researchers make NeoVax by first scanning the sequence of DNA in a patient’s tumor so they can identify the key epitopes within the cell neoantigens. Those epitopes serve as targets for the body’s T cells, the immune system’s main weapon against cancer.

Once a patient gets their NeoVax shot, the epitopes spark an immune system response against melanoma cells carrying those proteins.

NeoVax ‘remembers’ how to kill cancer

After four years, all eight patients on NeoVax were still alive and six showed no signs of the disease.

When study authors analyzed the group’s T cells, they uncovered evidence that the cells not only “remembered” their initial target epitopes, but also recognized other melanoma epitopes. Two of the patients, whose cancers had spread to their lungs, also received an immune checkpoint inhibitor. This drug loosens some of the restraints the immune response has when fighting cancer.

With those two patients, researchers found signs that their T cells had made their way into the tumor tissue. This is where the cancer-fighters can be most lethal to melanoma cells.

“We found evidence of everything we look for in a strong, sustained immune response,” study co-leader Dr. Patrick Ott reports. “T cells continued to specifically target melanoma cells and retained a memory of the epitopes they initially responded to. The T cells were activated to kill tumor cells and, critically, had diversified to target melanoma epitopes not included in the original vaccine.”

“The long-term persistence and expansion of the melanoma-targeting T cells is a strong indication that personal neoantigen peptide vaccines can help control metastatic tumors, particularly when combined with immune checkpoint inhibition,” Ott adds.

The findings appear in the journal Nature Medicine.

SWNS writer Stephen Beech contributed to this report.

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