Mining the melanosome for tumor vaccine targets: P.polypeptide is a novel tumor-associated antigen.
To identify novel, tumor-specific target antigens for vaccine development, we studied immune responses to P.polypeptide, an M(r) 110,000 integral melanosomal membrane protein associated with the Prader-Willi syndrome. Together with expressed sequence tag (EST) and serial analyses of gene expression (SAGE) library analyses, reverse transcription-PCR and Northern blotting verified that P.polypeptide expression was limited to melanoma and melanocytes. A single dominant epitope corresponding to positions 427-435 (IMLCLIAAV) was identified using allele-specific epitope forecasting combined with work in HLA-A*0201/K(b) transgenic mice. This epitope was then used to generate de novo human P.polypeptide-specific CD8+ T cells capable of recognizing P.polypeptide expressing human tumor cell lines in an HLA-A*0201-restricted fashion. Thus, P.polypeptide may be valuable in the creation of novel therapeutic anticancer vaccines.
Touloukian
C E
CE
Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892.
Leitner
W W
WW
Robbins
P F
PF
Rosenberg
S A
SA
Restifo
N P
NP
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020460:Melanosomes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C440848:P.polypeptide; D010455:Peptides; D012333:RNA, Messenger