title: NY-ESO-1 and LAGE-1 cancer-testis antigens are potential targets for immunotherapy in epithelial ovarian cancer.
abstract: Cancer-testis (CT) antigens are expressed in a variety of cancers, but not in normal adult tissues, except for germ cells of the testis, and hence appear to be ideal targets for immunotherapy. In an effort to examine the potential of NY-ESO-1 and LAGE-1 CT antigens for immunotherapy in epithelial ovarian cancer (EOC), we examined the expression of these antigens by reverse transcription-PCR (RT-PCR) and immunohistochemistry (IHC) in a large panel of EOC tissues and cell lines. Sera from a subgroup of the patients were tested for NY-ESO-1/LAGE-1 antibody by ELISA. The data indicated that four ovarian cancer cell lines were positive for one or both CT antigens. Expression of NY-ESO-1 in EOC was demonstrated by RT-PCR and/or IHC in 82 of 190 (43%) specimens. NY-ESO-1 expression by IHC ranged from homogeneous to heterogeneous pattern. LAGE-1 mRNA expression was present in 22 of 107 (21%) tumor tissues. Overall, the expression of either NY-ESO-1 or LAGE-1 mRNA was present in 42 of 107 (40%) EOC specimens and coexpression of both antigens was demonstrated in 11% of specimens. Antibody to NY-ESO-1/LAGE-1 was present in 11 of 37 (30%) patients whose tumors expressed either NY-ESO-1 or LAGE-1. Detectable antibodies were present for up to 3 years after initial diagnosis. Although there was no statistically significant relation between expression of NY-ESO-1/LAGE-1 antigen and survival, the data showed aberrant expression of NY-ESO-1 and LAGE-1 by IHC/RT-PCR in a significant proportion of EOC patients. These findings indicate that NY-ESO-1 and LAGE-1 are attractive targets for antigen-specific immunotherapy in EOC.
authors.affiliation: Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stockert
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tammela
authors.forename: Marilyn
authors.initials: M
authors.lastname: Intengan
authors.forename: Amy
authors.initials: A
authors.lastname: Beck
authors.forename: Bernadette
authors.initials: B
authors.lastname: Keitz
authors.forename: Darren
authors.initials: D
authors.lastname: Santiago
authors.forename: Barbara
authors.initials: B
authors.lastname: Williamson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Scanlan
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Deborah
authors.initials: D
authors.lastname: Driscoll
authors.forename: Ashwani
authors.initials: A
authors.lastname: Sood
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000097:blood; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D011379:Prognosis; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger