MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma.
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-A1(96-104), MAGE-A10(254-262), and gp100(614-622)) are immunogenic when administered with GM-CSF in Montanide ISA-51 adjuvant. T cells secreting IFN-gamma 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-A1(96-104), MAGE-A10(254-262), and gp100(614-622) 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-A1(96-104) and MAGE-A10(254-262) peptides may be considered for inclusion in vaccines against cancers of other histologic types, in addition to melanoma.
Chianese-Bullock
Kimberly A
KA
Department of Surgery/Division of Surgical Oncology, University of Virginia Health System, Charlottesville, VA 22908, USA.
Pressley
Jennifer
J
Garbee
Courtney
C
Hibbitts
Sarah
S
Murphy
Cheryl
C
Yamshchikov
Galina
G
Petroni
Gina R
GR
Bissonette
Eric A
EA
Neese
Patrice Y
PY
Grosh
William W
WW
Merrill
Priscilla
P
Fink
Robyn
R
Woodson
Elizabeth M H
EM
Wiernasz
Catherine J
CJ
Patterson
James W
JW
Slingluff
Craig L
CL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D009829:Oleic Acids / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D058951:gp100 Melanoma Antigen
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; C119317:MAGE-A10 antigen; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009829:Oleic Acids; C548637:PMEL protein, human; D010446:Peptide Fragments; D017778:Vaccines, Combined; D022223:Vaccines, Subunit; D058951:gp100 Melanoma Antigen; C477385:montanide ISA 51; D008353:Mannitol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor