Researchers make inroads in combination immunotherapy for melanoma

New York - Melanoma-derived peptide vaccines are currently an exciting area of melanoma immuno-therapy research, according to Douglas J. Schwartzentruber, M.D., medical director and director of the Center for Cancer Care at Goshen Health System, Goshen, Ind., speaking at the Society of Surgical Oncology annual meeting.

One vaccine that looks especially promising is the GP-100 peptide vaccine, developed by Dr. Stephen Rosenberg at the National Cancer Institute. The peptide and the HLA-A2 antigen are targets for T-cell recognition.

"A phase 2 trial of GP-100 vaccine plus interleukin-2 (IL-2, Chiron) showed a regression that was double that of the historical control of IL-2 alone," says Dr. Schwartzentruber. "The GP-100 vaccine attempts to develop an immune response against a protein commonly present on the surface of melanoma tumors."

So far, IL-2, recombinant cytokine and T-cell growth factor are showing encouraging results as a single-agent therapy in a small percentage of patients. Though no randomized clinical trials have been performed, IL-2 alone can lead to durable complete regression of metastatic disease in 7 percent of patients, and an additional 8 percent experience a partial disease regression. One limitation to the IL-2-based treatment is its high toxicity. Because of that, Dr. Schwartzentruber stresses that it should be limited to patients with a good performance status.

Although patients achieved a higher response with one vaccine combined with high-dose IL-2 in one study, the vaccine alone is not powerful enough to cause cancer regression.

Currently, a prospective phase 3 trial is under way comparing two treatment arms: IL-2 and no vaccine versus IL-2 plus the vaccine. The multicenter trial is currently recruiting. So far, 71 patients are enrolled, and the study has a target recruitment of 185.

Cellular therapies Early studies of lymphodepleting chemotherapy using T-cells and IL-2 are also encouraging. The strategy is based on extracting T-cells derived from the patient's own tumor biopsies, expanding them and administering following lymphodepleting chemotherapy along with the cytokine IL-2. This technique is also known as adoptive T-cell therapy. What is necessary is for the acquired T-cells to travel to the tumor site and survive there. For the immunotherapy strategy to work effectively, it must be able to stimulate the patient's transferred cells and immune system to kill or suppress the tumor cells - and in so doing, stop tumor progression.

An early trial led by Dr. Steven Rosenberg at the National Institutes of Health and presented separately at the Society of Surgical Oncology meeting has shown a 50 percent response rate. In a series of 32 patients, 16 responded to the lymph depletion chemotherapy approach, according to Dr. Schwartzentruber.