In the next 5 to 10 years, we may have the answer to the question of whether vaccines can fulfill their promise to become an effective treatment for melanoma, predict Brian J. Czerniecki, md, PhD, and Isabelle Bedrosian, md, in the latest issue of The Melanoma Letter, a publication of The Skin Cancer Foundation. These researchers are experimenting with a new kind of vaccine to combat disseminated melanoma.
In contrast to vaccines based on nonspecific immune stimulators, such as bacillus Calmette-Guerin (BCG), or on whole tumor cells, the scientists are focusing on peptides, a portion of the tumor cell. Peptides are amino acid groups associated with the antigens on melanoma cells that induce an immune response.
In a report on the new melanoma-derived peptide vaccines, Drs. Czerniecki and Bedrosian claim that these vaccines offer a number of potential advantages:
- They can be produced in large quantities and standardized.
- They are more effective than other vaccines in activating an immune response to specific melanoma antigens.
- They provide higher levels of antigen than can be obtained from whole tumor cells.
The strategy used in developing these vaccines is predicated on harnessing the unique immunologic functions of dendritic cells. These cells, also known as antigen-presenting cells, are extremely efficient at inducing T-cell responses. The T cells, which mediate the immune reaction, can recognize the peptides. When dendritic cells treated with peptide antigens derived from mouse tumors were administered to mice that had the same kind of tumors, cures were reported.
Optimal Vaccination Strategy Still to Be Determined
With the discovery of tumor-derived melanoma antigens, specific vaccines are under development for advanced melanoma, state Dr. Czerniecki, assistant professor, and Dr. Bedrosian, clinical research fellow, Department of Surgery, University of Pennsylvania, Philadelphia. However, the optimal vaccination strategy has yet to be determined.
The dendritic cells are especially suitable for antigen delivery. In studies conducted by the authors, dendritic cells treated with the peptides derived from the melanoma antigen known as MART-1/Melan A (melanoma antigen recognized by T lymphocytes) showed a great capacity to activate the T-cells.
Clinical studies assessing dendritic cell vaccines are now underway and, according to a preliminary report presented at the Fourth World Conference on Melanoma, clinical regressions were induced in 4 of 9 patients treated. Two of them had a complete response with regression of all evaluable disease, report Drs. Czerniecki and Bedrosian.