University of Pittsburgh Cancer Institute (UPCI) investigators have begun vaccinating people with advanced melanoma using molecules that are overexpressed in melanoma cells.
Unlike a vaccine that is given to prevent disease or the recurrence of a cancer, this vaccine is being used against established cancer in the hope that it will stimulate the patient's immune system to 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 strengthen it," said Walter Storkus, PhD, laboratory principal investigator of the study and associate professor in the departments of surgery and molecular genetics and biochemistry at the University of Pittsburgh Medical Center.
"This trial differs from the vast majority of other vaccine trials for melanoma because we are vaccinating individuals with part of a specific melanoma protein, or peptide, rather than with whole melanoma cells," said John Kirkwood, MD, a coprincipal investigator of the study, professor of medicine and chief of medical oncology at the University of Pittsburgh and director of the Pittsburgh Cancer Institute's Melanoma Center. "This precision will allow us to learn which of these marker peptides best triggers an immune response against the disease."
The peptides being evaluated are Melan-A and gp 100, whose functions are unknown, and tyrosinase, an enzyme involved with pigment formation. All three molecules are normally found in melanocytes, but their production is greatly increased in melanoma.
The two-month trial involves 36 patients divided into three groups of 12. Each group will receive four weekly injections of either Melan-A, gp 100 or tyrosinase, along with an immune stimulant called MF-59 (provided by Chiron, Inc.).
At the end of the sixth week, the investigators will assess the immunologic effect of the vaccine by determining whether treated patients develop a skin reaction to the peptide against which they were vaccinated. Also, the researchers will withdraw patient blood to test immune cells for reactivity against the peptides.
At the clinical level, the investigators will measure the cancer's response to treatment and will track disease progression, as well as overall long-term survival.
"Preclinical data strongly suggest that such tumor-derived peptides can be used to induce the immune system to shrink, or in some cases completely eliminate, cancers in mice," said Michael Lotze, MD, coinvestigator of the study. This clinical research is currently being conducted at two other research institutions--the National Institutes of Health in Bethesda, and, in conjunction with the Ludwig Institute for Cancer Research in Brussels, Belgium, and Lausanne, Switzerland.