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* Department of Surgery/Division of Surgical Oncology,
Cancer Center,
Department of Health Evaluation Sciences,
Department of Medicine/Division of Hematology-Oncology, and
¶ Department of Pathology, University of Virginia Health System, Charlottesville, VA 22908
Twelve peptides derived from melanocyte differentiation proteins and cancer-testis Ags were combined and administered in a single mixture to patients with resected stage IIB, III, or IV melanoma. Five of the 12 peptides included in this mixture had not previously been evaluated for their immunogenicity in vivo following vaccination. We report in this study that at least three of these five peptides (MAGE-A196104, MAGE-A10254262, and gp100614622) are immunogenic when administered with GM-CSF in Montanide ISA-51 adjuvant. T cells secreting IFN-
in response to peptide-pulsed target cells were detected in peripheral blood and in the sentinel immunized node, the node draining a vaccine site, after three weekly injections. The magnitude of response typically reached a maximum after two vaccines, and though sometimes diminished thereafter, those responses typically were still detectable 6 wks after the last vaccines. Most importantly, tumor cell lines expressing the appropriate HLA-A restriction element and MAGE-A1, MAGE-A10, or gp100 proteins were lysed by corresponding CTL. This report supports the continued use of the MAGE-A196104, MAGE-A10254262, and gp100614622 epitopes in peptide-based melanoma vaccines and thus expands the list of immunogenic peptide Ags available for human use. Cancer-testis Ags are expressed in multiple types of cancer; thus the MAGE-A196104 and MAGE-A10254262 peptides may be considered for inclusion in vaccines against cancers of other histologic types, in addition to melanoma.
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