PHILADELPHIA--Lymphocytes are known to infiltrate melanoma lesions
at the primary site, occasionally resulting in spontaneous regressions.
Therefore, investigators in search of specific treatments for
metastatic melanoma have turned to immunologic approaches, John
Kirkwood, MD, said at the 12th Annual Toward 2000 Symposium at
Fox Chase Cancer Center.
Some of Dr. Kirkwood's studies at the University of Pittsburgh's
Melanoma Center focus on antigens that elicit antibody responses,
such as gangliosides on tumor cell surfaces. However, he said,
the critical issue is whether a vaccine will elicit a T cell response,
and in this regard peptide antigen vaccines appear to be good
Peptide antigens fall into two categories, Dr. Kirkwood said.
Representative of the first are melan A or MART-1 (melanoma antigen
recognized by T cells) and tyrosinase, a pigmenting enzyme of
the melanocyte lineage. These are lineage markers of melanoma
and melanocytes, and are found in few other tissues.
MAGE-1 and MAGE-3
The second category of peptide antigens is characterized by MAGE-1,
MAGE-3, and other antigens that are cancer-associated and found
in no normal tissues except in the testis. These molecules are
enfolded on the surface of tumor cells within HLA molecules.
Working with Dr. Kirkwood and Michael T. Lotze, MD, at the University
of Pittsburgh, Walter Storkus, PhD, has been able to elute molecules
from the HLA and define a series of peptide antigens that are
recognized by T cells in association with specific HLA types.
Since at least half of the population has tissue type HLA A2,
the initial studies involve three peptides recognized by the immune
cells of these patients: MART-1, gp100, and tyrosinase.
Patients are randomized to one of these peptides, and are immunized
once weekly for 4 weeks with peptide combined with MF59, an oil
adjuvant to increase immune response.