Certain tumor markers for melanoma could signal best results for vaccine

Scientists at the John Wayne Cancer Institute (JWCI) in Santa Monica, California have found a panel of molecular markers that could signal which patients might have the best results following vaccination for malignant melanoma.

According to a study published in the January 15, 2003 issue of Cancer Research, a journal of the American Association for Cancer Research (AACR), the scientists showed that patient survival improved significantly if their tumors expressed higher levels for these markers, known as melanoma-associated antigens (MAAs).

“This investigation has provided a major clue why a certain subset of advanced melanoma patients, about 10 percent of these patients, survive longer than others,” said Dr. Dave S. B. Hoon, director of molecular oncology at the JWCI and the study’s principal investigator.

“It also indicates that active-specific immunotherapy such as vaccines against melanoma may be particularly effective in this same group of patients.”

More than 40,000 new cases and 7,000 deaths will occur this year in the U.S. from melanoma, the most serious form of skin cancer. As such, it is the fifth most common cancer in the nation.

If diagnosed and treated early, the cure rate for melanoma is high. But if it is not removed at an early stage, cancer cells may grow and invade healthy tissue below the skin surface and spread to other parts of the body. The most advanced form of the disease, stage IV tumors that spread to distant organs, has proved resistant to standard treatments of chemo- and radiotherapy. The five-year survival rate among these patients is about five percent.

For this reason, new approaches are under investigation including the use of melanoma vaccines that enhance the body’s immune response to specific protein melanoma-associated antigens expressed by tumors.

In their study, funded by the National Institutes of Health and the National Cancer Institute, the JWCI scientists surgically removed tumor samples from 35 late-stage melanoma patients, of which 30 then received immunotherapy with CANVAXIN, a cancer vaccine (CancerVax Corp., of Carlsbad, Calif.).

The tumors subsequently were analyzed for three immunogenic MAAs — TYR, TRP-2 and MART-1 — all contained in the cancer vaccine. To assist with their analysis, the scientists turned to a relatively new technique, quantitative reverse-transcriptase Real Time polymerase chain reaction (qRT) analysis ? a rapid and highly sensitive procedure invented by Dr. Hoon that magnifies the presence of molecular tumor markers, including these MAAs. Patients were then followed for up to five years to see how their disease progressed.

The results showed that individuals whose tumors have lower expressions for at least two of the MAA markers had a significantly worse prognosis than their counterparts. Conversely, patients with elevated levels for two out of three MAA markers experienced improved survival outcomes.

The JWCI scientists suggested that these antigens enhance the body’s immune response to the vaccine, and thus potentially could be used in the clinic to help assess the treatment’s likelihood for success.

“It is likely that melanoma cells with decreased expression or loss of MAA are of a selected aggressive phenotype with greater advantage to progress and escape host immunity, thus adversely affecting patients’ overall survival,” said Dr. Hoon.

“These studies suggest that advanced staged patients with melanomas expressing the two or three of the MAAs would benefit from surgery followed by adjuvant active-specific immunotherapy targeting of these MAAs.”

What’s more, the results indicate there are potential patients with advanced melanoma disease who can benefit from immunotherapy and that molecular diagnosis can play an integral role in identifying these patients. “The development of molecular stratification factors for specific treatment regimens in malignant melanoma is a major focus of our studies in the molecular oncology department at JWCI,” added Dr. Hoon.