In the study, the scientists used a small protein called a peptide found in approximately 70 percent of melanomas, but not in normal cells, to stimulate immune cells called killer T cells to attack the melanoma cells. Another type of immune cell called a monocyte was used to present the peptide, BRAFV600E, to the killer T cells to trigger their attack on the melanoma cells.
"In our experiments, we saw a strong cancer-killing immune response when killer T cells are stimulated with this peptide," says Dorothee Herlyn, D.V.M., senior author on the study and a professor in the Immunology Program and Molecular and Cellular Oncogenesis Program at Wistar. "The results emphasize the potential of this approach for creating an effective melanoma vaccine, and we hope to move toward human clinical trials as soon as possible."
A substantial proportion of melanoma patients, about 50 percent, have killer T cells able to recognize the BRAFV600E peptide. Combining the prevalence of the peptide among melanoma patients – about 70 percent – with the number of patients whose immune cells are able to respond to the peptide suggests that a vaccine based on BRAFV600E could treat approximately a third of all melanoma patients.
Herlyn adds that the specificity of the peptide – the fact that it is found only in melanoma cells, not normal cells – suggests that the toxicity of any vaccine based on the peptide would be minimal. Killer T cells sparked into action by the vaccine would target only the cancer cells, sparing healthy cells entirely.
Looking ahead to possible human clinical trials, another member of the scientific team, University of Pennsylvania assistant professor Brian Czerniecki, M.D., Ph.D., is working to prepare yet another type of immune cell, called a dendritic cell, to present the BRAFV600E peptide to killer T cells. Dendritic cells have as their primary job the presentation of foreign materials to the immune system, and the expectation is that dendritic cells presenting the BRAFV600E peptide would trigger the killer T cells even more effectively than the monocyte cells used in the current study. Indeed, such prepared dendritic cells might serve as the basis for a treatment vaccine that could be taken into human clinical trials.
Herlyn is senior author on the Cancer Research study. The lead author is Rajasekharan Somasundaram, also at Wistar. The additional Wistar coauthors are Rolf Swoboda, Laura Caputo, and Laszlo Otvos (now at Temple University). The remaining coauthors are Barbara Weber, Patricia Volpe, Patricia van Belle, Susan Hotz, David E. Elder, Lynn Schuchter, DuPont Guerry, and Brian J. Czerniecki of the University of Pennsylvania, and Francesco M. Marincola with the National Institutes of Health.
Support for the research was provided by the National Institutes of Health and the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health.
The Wistar Institute is an independent nonprofit biomedical research institution dedicated to discovering the causes and cures for major diseases, including cancer, cardiovascular disease, autoimmune disorders, and infectious diseases, including AIDS and influenza. Founded in 1892 as the first institution of its kind in the nation, The Wistar Institute today is a National Cancer Institute-designated Cancer Center focused on basic and translational research. Discoveries at Wistar have led to the creation of vaccines for such diseases as rabies, rubella, and rotavirus; significant insights into the mechanisms of skin, brain, breast, lung, and prostate cancers; and the development of monoclonal antibodies and other significant research technologies and tools. News releases from The Wistar Institute are available to reporters by direct e-mail upon request.
Journal
Cancer Research