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Personal neoantigen vaccine prompts lasting response in melanoma patients


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Journal
Nature Medicine online
Reuters Health - 05/02/2021 - A small number of high-risk melanoma patients have continued to show durable CD4+ and CD8+ T cell responses against the majority of immunizing epitopes originally prompted by receipt of NeoVax, a vaccine targeting multiple personal neoantigens, according to an international group of researchers.

"We found vaccine-specific T cells that persist in the peripheral blood of melanoma patients for years and are able to traffic to metastatic tumors," Dr. Patrick A. Ott of Dana-Farber Cancer Institute, in Boston, told Reuters Health by email. "This observation supports the ability of personal neoantigen vaccines to induce durable cancer specific immunity, a critical prerequisite for long-term tumor control."

In a paper in Nature Medicine, Dr. Ott and colleagues note that they previously demonstrated that this personal neoantigen long-peptide vaccine was feasible, safe and immunogenic in patients with high-risk melanoma.

A separate study showed that this was also the case in patients with glioblastoma. These and other results testing personal neoantigen-directed vaccines, they say, are encouraging. However, so far, only relatively short-term immune responses have been reported.

Thus, the researchers evaluated the long-term clinical outcome and circulating immune responses of eight patients with advanced melanoma. The patients had undergone surgery with curative intent but were considered at high risk of recurrence.

A median of 18 weeks after surgery, following specific tumor-DNA sequencing to identify the key epitopes within the tumor-cell neoantigens, the patients received NeoVax. None had measurable disease at the time of vaccine initiation.

At a median follow-up of 55 months after surgery all were still alive and six had no evidence of disease. Two of the patients whose disease had spread received subsequent anti-PD-1 therapy with pembrolizumab. One patient developed two additional non-vaccine antigen-directed responses after this therapy.

That and other findings, say the researchers, indicate "epitope spreading that is detectable early after vaccination, can extend to additional targets after anti-PD-1 therapy, and that persists for several years."

"We found evidence of everything we look for in a strong, sustained immune response," Dr. Ott said in a statement. "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," he concluded, "is a strong indication that personal neoantigen peptide vaccines can help control metastatic tumors, particularly when combined with immune checkpoint inhibition."

The researchers have filed patent applications related to their work.

SOURCE: https://go.nature.com/36nHnPH Nature Medicine online, January 21, 2021.

By David Douglas



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