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
"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.