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
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.