Melanoma vaccine shows promise

Main Category: Melanoma / Skin Cancer
Article Date: 31 Oct 2003 - 0:00 PDT

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Contact: Bob Beard
reb8e@virginia.edu
434-982-4490
University of Virginia Health System

CHARLOTTESVILLE, Va. - A multi-peptide vaccine to treat melanoma resulted in an immune response from 75 percent of the patients and is associated with tumor regression, according to a randomized, phase II clinical trial involving more than two dozen patients with advanced melanoma at the University of Virginia Health System.

The trial also reveals what may be the most effective treatment regimen to activate an immune response from the body against melanoma. The results are published in the Nov. 1 edition of the Journal of Clinical Oncology found online at www.jco.org.

Melanoma is the most serious form of skin cancer. According to the American Cancer Society, more than 53,000 new cases of the disease are expected this year, and about 7,400 people will die of melanoma. Peptides are molecules consisting of two or more amino acids linked by a peptide bond.

'There have been significant tumor regressions on this protocol of peptide vaccines against melanoma,' said Dr. Craig L. Slingluff, Jr., professor of surgery and director of the Human Immune Therapy Center at U.Va. 'This gives us hope that this approach may be useful for patients with advanced disease.'

In the trial, 26 patients with stage III or IV melanoma received six vaccinations of a mixture of four melanoma peptides developed at U.Va., followed by a tetanus helper peptide and low-dose interleukin-2.

In one-half of the patients, the peptides were injected in an emulsion including a cytokine called granulocyte macrophage-colony stimulating factor (GMCSF.) In the other half, the peptides were injected after being pulsed on dendritic cells.

The results showed that the immune response against melanoma was greater in patients vaccinated with the GMCSF emulsion. Responses by the immune system's killer or cytotoxic t-cells were observed in the lymph nodes draining the vaccine site in 80 percent of patients on the GMCSF arm, and in the peripheral blood of 42 percent of the GMCSF patients.

However, t-cell responses were observed in the lymph nodes of only 13 percent of the patients vaccinated with dendritic cells and 11 percent of those patients' peripheral blood.

Partial clinical responses, including tumor shrinkage, were seen in four of the 13 patients injected with the GMCSF emulsion. Two patients experienced stable disease for several months. Favorable outcomes were observed in two of the 13 patients on the dendritic cell arm. The only serious side effect was hyperglycemia in one patient. Other side effects included fatigue, weight loss, nausea and injection-site reaction.

'Peptide vaccines for cancer can induce an immune response in the body against the cancer cells with minimal toxicity, but so far there is no consensus about how best to vaccinate patients,' said Slingluff. 'Results from this U.Va. clinical trial seemed to show that the GMCSF emulsion is most effective. Multi-peptide vaccines with this emulsion warrant continued investigation.'

Slingluff and the team of U.Va. scientists have kept the GMCSF arm of the melanoma vaccine trial open, and have offered booster vaccines to some patients with evidence of tumor regression or stable disease. They also are evaluating the impact of low-dose interleukin-2 combined with the melanoma vaccine on t-cell responses.

Nearly all skin cancers can be prevented by limiting sun exposure. The American Cancer Society recommends the 'slip, slop, slap, wrap' method of prevention. Slip on a shirt, slop on sunscreen of 15 SPF or higher, slap on a hat and wrap on sunglasses before going out on sunny days.