Identification of HLA-A*0201-restricted CTL epitopes encoded by the tumor-specific MAGE-2 gene product.
MAGE-2 is expressed in many tumors, including melanoma, laryngeal tumors, lung tumors and sarcomas, but not in healthy tissue, with the exception of testis. Thus, MAGE-2-derived peptides that bind to HLA class I molecules and elicit cytotoxic T lymphocyte (CTL) responses could be of significant therapeutic importance. In this study, we show that several MAGE-2-derived peptides bind with high affinity to HLA-A*0201. Three of them form complexes with HLA-A*0201 that are stable at 37 degrees C and are immunogenic in HLA-A*0201Kb transgenic mice. Moreover, CTLs against 2 of them (M2 112-120, and M2 157-166) specifically recognize cells that express both the MAGE-2 protein and HLA-A*0201Kb. These 2 peptides are processed and presented in the context of HLA-A*0201. Therefore, these peptides are candidate components in peptide-based vaccines for the treatment and prevention of several types of MAGE-2-expressing cancers.
Visseren
M J
MJ
Department of Immuno-hematology and Blood Bank, Leiden University Hospital, The Netherlands.
van der Burg
S H
SH
van der Voort
E I
EI
Brandt
R M
RM
Schrier
P I
PI
van der Bruggen
P
P
Boon
T
T
Melief
C J
CJ
Kast
W M
WM
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019556:COS Cells; D019496:Cancer Vaccines / Q000627:therapeutic use; D000939:Epitopes; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D015234:HLA-A Antigens; C072012:MAGEB2 protein, human; C512965:Mageb2 protein, mouse; D009363:Neoplasm Proteins