UF immunologist seeks patent for vaccine against melanoma skin cancer

September 1, 2005

GAINESVILLE, Fla. — A vaccine against melanoma – the most deadly form of skin cancer – provides almost complete protection in mice and could lead to a similar treatment for people, according to a University of Florida immunologist who has developed a novel treatment for the cancer.

The vaccine uses inactivated or dead melanoma cells in combination with a super-antigen to boost the immune response in mice against malignant melanoma cells, said Howard Johnson, a professor of immunology at UF’s Institute of Food and Agricultural Sciences. Super-antigens are proteins that are potent stimulators of cells of the immune system.
He said UF is in the process of obtaining patent protection for the vaccine and licensing the technology to a pharmaceutical company. Once the vaccine is licensed, human clinical trials can begin, a process that could take three or four years.

“Until now, super-antigens have never been used in a cancer vaccine, and our research shows that these proteins help provide a strong immune response against malignant melanoma,” said Johnson, an internationally recognized immunologist who was the first to show that molecules called interferons are important regulators of the immune system.

“We have found that combinational therapy of super-antigens and inactivated melanoma cells can protect 60 to 100 percent of the mice against a 25-fold lethal dose of melanoma,” Johnson said. “More importantly, when vaccinated mice were challenged a half-year later with a lethal melanoma dose, 80 to 100 percent survived the second challenge, which is essentially complete protection.”

He said these preclinical studies demonstrate that weak immune responses against cancers such as melanoma can be converted to strong responses by using super-antigens in the vaccine. Moreover, preventive or prophylactic vaccination against cancer would be more effective than attempting to develop a vaccination against existing cancer.

“For the sake of comparison, we know that vaccination against active flu or polio is not effective, but preventive vaccination can give the immune system a head start against these and other diseases,” Johnson said. “When it comes to slowing or stopping melanoma, this head start has clearly been the difference between life and death in our mice models.”

He said that melanoma cancer cells do produce an immune response, but the response is too weak to mount an effective defense against the cancer under normal circumstances.

“This is because the proteins on the surface of a melanoma cell are not as ‘foreign’ to us as those of influenza and polio viruses, so we are using proteins called super-antigens to boost the immune response to melanoma – our approach is to use super-antigens to enhance the response to a point where melanoma cells are killed.”

Johnson’s vaccine would primarily benefit two groups of people: the elderly and those who have already had a melanoma lesion.

“As we age, we become more at risk for developing melanoma and other cancers,” he said. “People who have had melanoma lesions successfully removed are at greater risk of developing future lesions, so vaccination should reduce the risk of recurrence,” he said.

Dr. John Carucci, director of Mohs micrographic and dermatologic surgery at Weill Medical College of Cornell University in New York City, said Johnson’s concept, as presented, is exciting.

“Most studies have been concerned with developing vaccines against existing cancers rather than the prophylactic model,” Carucci said. “The idea of using super-antigens to boost immune response is interesting, but I would need to see the data in order to evaluate the study. A growing body of evidence supports the potential role of the immune system in regulating the pathogenesis of melanoma, and it’s likely that this research provides additional food for thought – I would be very interested in reviewing the data.”

Johnson said malignant melanoma is an aggressive form of cancer derived from melanocytes in normal skin. Currently, melanoma accounts for about 4 percent of all newly diagnosed cancers in the United States with more than 53,000 new cases and about 7,400 deaths annually.

According to an article published last month in the British Medical Journal, the rates of melanoma skin cancer are rising because more doctors are screening people for skin cancer, not because the cancer is becoming more common.

Early-stage lesions are curable by surgical removal, but once melanoma spreads to distant sites by the lymphatic system, the prognosis is guarded. It has been estimated that 8 to 15 percent of melanoma patients will be diagnosed with central nervous system metastases, which are particularly difficult to treat.

“In fact, metastasized, advanced melanoma is generally unresponsive to chemotherapy, which has little or no effect on overall survival,” Johnson said. “With the relative resistance of melanoma to chemotherapy, alternative approaches to therapy, in particular immunotherapies, are needed.”