Melanoma Vaccine from NeoVox Shows Anti-Tumor Response Four Years Later

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Researchers at The University of Texas MD Anderson Cancer Center have found that a rare resistance mutation first thought to appear in melanoma (pictured) following treatment with a targeted therapy has instead turned out to be hiding in the tumor all along. [Definiens]

In encouraging news regarding melanoma therapy, researchers found that a personalized vaccine continues to keep cancer cells in check four years after patients received it.

In a Phase 1 study among eight patients with advanced melanoma who received the NeoVax vaccine, after a median of four years, all of the patients were alive. Six patients had no signs of active disease. Further, studies of patients’ T cells revealed they were still active against their originally targeted proteins on melanoma cells but also recognized others.

Two patients who had cancer metastases to their lungs also received treatment with pembrolizumab, an immune checkpoint inhibitor, along with the NeoVax vaccine. The researchers found activated T cells within their tumor tissues. The results of this long-term analysis are published in Nature Medicine today.

“We found evidence of everything we look for in a strong, sustained immune response,” says the study’s co-lead investigator Patrick A. Ott, MD, PhD, of Dana-Farber Cancer Institute, Brigham and Women’s Hospital (BWH), and the Broad Institute. Ott developed the NeoVax concept along with colleague Catherine Wu, MD of Dana-Farber.

“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,” says Ott. “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.”

DNA sequencing of the patient’s tumor reveals key abnormal proteins, called neoantigens, made only by cancer cells. They result from DNA mutations associated with cancers.

The NeoVax vaccine is made from pieces of up to 20 of these abnormal proteins.  Each patient’s tumor expresses its own unique neoantigens on its cells’ surfaces which trigger the T cells of the immune system to respond.  The vaccine is designed to stimulate two kinds of T-cells – CD8+killer cells and CD4+ helper cells.

The neoantigen targets essentially wave a flag alerting circulating T-cells to their presence, leading them to diseased cells. Since only cancerous cells produce these neoantigens, normal cells should not come under T cell attack.  To boost the immune system further, the NeoVax vaccine also contains a biochemical adjuvant.

In this study, NeoVax was given to patients 18 weeks after surgery for advanced melanoma and followed for several years. These results follow an earlier analysis at approximately 25 months with similar findings.

The NeoVax vaccine concept is also in early clinical studies for glioblastoma and kidney cancer.

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