by Dr. C.H. Weaver M.D.

Four years after patients with melanoma were treated with a personalized cancer vaccine, the immune response kindled by the vaccine remains robust and effective in keeping cancer cells under control according to researchers at Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and the Broad Institute of MIT.

Research has long suggested that the use of a patient’s own immune cells may be a key to treating melanoma.(2,3) Immune cells mixed with certain proteins have preeviously been shown to produce an immune response against the melanoma when re-infused back into the patient resulting in long term remissions.

The findings from the current study, published online by the journal Nature Medicine, demonstrate the staying power of the immune response generated by the vaccine, known as NeoVax, which works by targeting specific proteins on each patient’s tumor cells. The researchers found that, nearly four years after vaccination, the patients’ immune system cells were active not only against tumor cells with those distinctive proteins, but also spread to other proteins found in those patients’ tumor cells.

The study involved eight patients at high risk of recurrence following surgical removal of their melanoma. The vaccine is made from bits of proteins, called epitopes, that poke from the cell surface and serve as signals to the immune system. The epitopes come from neoantigens which are abnormal proteins on the cancer cells that warn that a cell is cancerous and should be destroyed. To make the vaccine the sequence of DNA in each patient’s cancer is scanned to identify targets for T cells, which lead the immune system’s attack on the cancer.

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Researchers reported that a median of four years after treatment, all eight patients survived with six showing no signs of active disease. They also found evidence that the cells not only “remembered” their initial target epitopes but had expanded their repertoire to recognize other melanoma-related epitopes as well. The researchers reported that they found evidence of a sustained immune response. 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 cancer cells and, critically, had diversified to target melanoma epitopes not included in the original vaccine.

These findings demonstrate that a personal neoantigen vaccine can stimulate a durable immune response in patients with melanoma, and that 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. Dana Farber researchers have also evaluated the Neovax vaccine in kidney cancer.

References:

  1. Vaccine produces long-lasting anti-tumor response in patients with melanoma
  2. Schwartzentruber DJ, Lawson D, Richards J et al. A phase III multi-institutional randomized study of immunization with the gp100:209-217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA9011.
  3. Hunder N, Wallen H, Cao J, et al. Treatment of Metastatic Melanoma with Autologous CD4+ T Cells Against NY-ESO-1. New EnglandJournal of Medicine. 2008;258:2698-2703.