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Researchers discover how to boost efficacy of vaccine to prevent melanoma recurrence

Researchers at Mount Sinai Hospital in New York found that a vaccine created to prevent the recurrence of melanoma can be twice as effective when patients also receive two additional components that boost the number of dendritic cells in their immune system.

Results of a phase 2 clinical trial were published online ahead of print in the journal Nature Cancer (Nov. 16, 2020).

According to investigators, the results of the clinical trial show that adding the small molecule Flt3L, which increases the number of dendritic cells, boosted the vaccine's effectiveness at inducing the production of antibodies and T cells that can later fight melanoma.

Further, the addition of a second component, called poly-ICLC, also strengthened the ability of the dendritic cells' to promote antibodies as well as helper and killer T cells.

Researchers at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, along with colleagues at the National Cancer Institute-funded Cancer Immunotherapy Trials Network (CITN) based at the Fred Hutchinson Cancer Research Center, found that adding the two immune-boosting components can increase the immune response for not only melanoma patients but possibly others whose cancers express similar antigens.

The results are important because most cancer vaccine trials have failed to show clinical efficacy, the study’s authors noted.

For the trial, 60 patients who had stage 2 or 3 melanoma, and whose cancer was successfully excised via surgery, received the vaccine. Half of the patients received the vaccine alone while the other half received the vaccine with Flt3L and poly-ICLC.

The vaccine was designed to target dendritic cells and is composed of an antigen found in melanoma bound to an antibody to increase the chances of binding with dendritic cells.

The cocktail of the vaccine, Flt3L, and poly-ICLC nearly doubled the vaccine's efficacy, according to analysis of the T cells detected in patients' blood samples after they received four doses over four months.

That immune response was seen significantly earlier in the patients who received the cocktail and at much higher levels in many more patients compared to those who received only the vaccine. Researchers found antibodies were still present in blood samples tested 12 weeks after the last dose.

"This is the first randomized clinical trial to show that an immune response to a cancer vaccine can be potentiated by the addition of Flt3L," said Dr. Nina Bhardwaj, in a press release. Dr. Bhardwaj is the director of the immunotherapy program at The Tisch Cancer Institute and the first author on the study. "The response was achieved because Flt3L mobilized dendritic cells, which are the gold standard in promoting cancer immunity, and improved the overall immunogenicity of the vaccine. This may change the approach of increasing efficacy in other cancer vaccines in the future."

The study’s authors note these findings also provide a basis for adding immunotherapies called checkpoint inhibitors, which have been successful in treating metastatic melanoma, to vaccines to further increase the success in fending off melanoma recurrence.

Researchers also plan to follow trial participants over time and measure how many have cancer recurrence to further study the vaccine’s efficacy in each group.

“Immunotherapy has already shown great promise for patients with metastatic melanoma who would normally have a difficult, sometimes grave, prognosis,” said Dr. Philip Friedlander. Dr. Friedlander is the director of the Melanoma Medical Oncology Program at The Tisch Cancer Institute at Mount Sinai and was a site investigator of the trial. “It is important to work toward developing effective cancer vaccines that can prevent cancer on their own or in addition to the drugs already available.”

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