University of Pittsburgh Researchers Use Dendritic Cells to Successfully Treat Experimental Cancers

Potent immune cells that have been pretreated with peptides takenfrom the surface of tumor cells are effective in curing establishedcancers and in preventing cancers from developing in mice, accordingto research published in the December 1995 issue of NatureMedicine. Clinical trials of this therapeutic approach willbegin soon, according to study investigators.

"We consider these findings extremely important because theystress that destruction of large tumors can be achieved solelythrough inducing an immune response against a single tumor peptide,"said Michael T. Lotze, MD, senior author of the study and professorof molecular genetics and biochemistry and co-director of theUniversity of Pittsburgh Cancer Institute's Biological TherapeuticsProgram.

The study involved mice that were transplanted with one of threetumors: lung cancer, melanoma, or sarcoma. Each group of micewas then intravenously injected with dendritic cells that hadbeen pretreated with a specific synthetic tumor peptide that hadbeen found to occur naturally on the surface of their cancer cells(lung, melanoma, or sarcoma).

Dendritic cells pick up tumor peptides during the pretreatmentprocess. These cells are considered "professionals"at capturing and presenting tumor peptides to killer T-cells,which attack tumor cells. Dendritic cells themselves also carrysurface molecules that are needed to costimulate killer T-cellstogether with tumor peptide.

The Pittsburgh researchers found that tumors disappeared in morethan 80% of animals in each of the three tumor groups. Dendriticcells pretreated with tumor peptides for a specific cancer wereeffective only against mouse tumors with that peptide. For example,dendritic cells pretreated with the tumor peptide taken from lungcancer cells effectively treated only mice with lung tumors.

Healthy mice that were vaccinated with the pretreated dendriticcells failed to develop cancer when they were later injected withtumor cells, suggesting that the mice developed a lasting immunityto specific cancers.

"This approach differs from any previously reported vaccinationstudies in that we have tightly linked the two essential ingredients--dendriticcells and tumor antigens--to stimulate killer T-cells and treatexperimental cancers," said Walter Storkus, PhD, co-investigatorof the study and assistant professor of molecular genetics andbiochemistry at the university.

"This is the first report that dendritic cells have the abilityto present a tumor peptide to the immune system and to invokesufficient killer T-cell-mediated immunity against that same peptide,"added Dr. Lotze.

"We have just received FDA approval to conduct early clinicaltrials of this cancer vaccine in patients with melanoma, for whichwe have already identified tumor peptides that stimulate killerT-cells," Dr. Lotze noted.