University of Pittsburgh Cancer Institute (UPCI) investigators have begun vaccinating people with advanced melanoma using molecules that are overexpressed in melanoma cells.
University of Pittsburgh Cancer Institute (UPCI) investigatorshave begun vaccinating people with advanced melanoma using moleculesthat are overexpressed in melanoma cells.
Unlike a vaccine that is given to prevent disease or the recurrenceof a cancer, this vaccine is being used against established cancerin the hope that it will stimulate the patient's immune systemto better detect and kill melanoma cells.
"Melanoma is one of the few cancers known to be immunogenic....In this trial, we hope to capitalize on this recognition and strengthenit," said Walter Storkus, PhD, laboratory principal investigatorof the study and associate professor in the departments of surgeryand molecular genetics and biochemistry at the University of PittsburghMedical Center.
"This trial differs from the vast majority of other vaccinetrials for melanoma because we are vaccinating individuals withpart of a specific melanoma protein, or peptide, rather than withwhole melanoma cells," said John Kirkwood, MD, a coprincipalinvestigator of the study, professor of medicine and chief ofmedical oncology at the University of Pittsburgh and directorof the Pittsburgh Cancer Institute's Melanoma Center. "Thisprecision will allow us to learn which of these marker peptidesbest triggers an immune response against the disease."
The peptides being evaluated are Melan-A and gp 100, whose functionsare unknown, and tyrosinase, an enzyme involved with pigment formation.All three molecules are normally found in melanocytes, but theirproduction is greatly increased in melanoma.
The two-month trial involves 36 patients divided into three groupsof 12. Each group will receive four weekly injections of eitherMelan-A, gp 100 or tyrosinase, along with an immune stimulantcalled MF-59 (provided by Chiron, Inc.).
At the end of the sixth week, the investigators will assess theimmunologic effect of the vaccine by determining whether treatedpatients develop a skin reaction to the peptide against whichthey were vaccinated. Also, the researchers will withdraw patientblood to test immune cells for reactivity against the peptides.
At the clinical level, the investigators will measure the cancer'sresponse to treatment and will track disease progression, as wellas overall long-term survival.
"Preclinical data strongly suggest that such tumor-derivedpeptides can be used to induce the immune system to shrink, orin some cases completely eliminate, cancers in mice," saidMichael Lotze, MD, coinvestigator of the study. This clinicalresearch is currently being conducted at two other research institutions--theNational Institutes of Health in Bethesda, and, in conjunctionwith the Ludwig Institute for Cancer Research in Brussels, Belgium,and Lausanne, Switzerland.