Potent immune cells that have been pretreated with peptides taken from the surface of tumor cells are effective in curing established cancers and in preventing cancers from developing in mice, according to research published in the December 1995 issue of Nature Medicine. Clinical trials of this therapeutic approach will begin soon, according to study investigators.
"We consider these findings extremely important because they stress that destruction of large tumors can be achieved solely through inducing an immune response against a single tumor peptide," said Michael T. Lotze, MD, senior author of the study and professor of molecular genetics and biochemistry and co-director of the University of Pittsburgh Cancer Institute's Biological Therapeutics Program.
The study involved mice that were transplanted with one of three tumors: lung cancer, melanoma, or sarcoma. Each group of mice was then intravenously injected with dendritic cells that had been pretreated with a specific synthetic tumor peptide that had been found to occur naturally on the surface of their cancer cells (lung, melanoma, or sarcoma).
Dendritic cells pick up tumor peptides during the pretreatment process. These cells are considered "professionals" at capturing and presenting tumor peptides to killer T-cells, which attack tumor cells. Dendritic cells themselves also carry surface molecules that are needed to costimulate killer T-cells together with tumor peptide.
The Pittsburgh researchers found that tumors disappeared in more than 80% of animals in each of the three tumor groups. Dendritic cells pretreated with tumor peptides for a specific cancer were effective only against mouse tumors with that peptide. For example, dendritic cells pretreated with the tumor peptide taken from lung cancer cells effectively treated only mice with lung tumors.
Healthy mice that were vaccinated with the pretreated dendritic cells failed to develop cancer when they were later injected with tumor cells, suggesting that the mice developed a lasting immunity to specific cancers.
"This approach differs from any previously reported vaccination studies in that we have tightly linked the two essential ingredients--dendritic cells and tumor antigens--to stimulate killer T-cells and treat experimental cancers," said Walter Storkus, PhD, co-investigator of the study and assistant professor of molecular genetics and biochemistry at the university.
"This is the first report that dendritic cells have the ability to present a tumor peptide to the immune system and to invoke sufficient killer T-cell-mediated immunity against that same peptide," added Dr. Lotze.
"We have just received FDA approval to conduct early clinical trials of this cancer vaccine in patients with melanoma, for which we have already identified tumor peptides that stimulate killer T-cells," Dr. Lotze noted.