Characterization of preexisting humoral immunity specific for two cancer-testis antigens overexpressed at the mRNA level in non-small cell lung cancer.
In order to establish a rationale for immunotherapy for lung cancer, we have investigated immunological characteristics of tumor-associated antigens (TAAs) discovered through molecular approaches. Preexisting Abs specific to these predicted TAAs were examined using specimens of lung pleural effusions (LPEs) and sera in non-small cell lung cancer (NSCLC) patients. The novel cancer-testis (CT) antigens L514S and L552S were highly expressed in approximately half of the NSCLC tissues and established cell lines examined. When lung cancer patients in the USA and Japan were screened, 13%, 17%, and 5% were found to have Abs specific to recombinant L514S, L552S, and NY-ESO-1 proteins, respectively, whereas 48 normal donors had no Abs to these three CT antigens. The Ab titers specific to recombinant L552S and L514S proteins were similar to, and slightly lower than, Abs specific to NY-ESO-1 in stage IV NSCLC patients. To further characterize the preexisting specific Abs, the epitopes were analyzed using 20-aa length peptides entirely covering both antigens. An epitope common to the patients' L514S-specific Abs was identified as aa 85-100 and multiple epitopes, including a major epitope (aa 141-160), were identified for L552S-specific Abs. The Ab epitopes thus identified are not found in human, animal, or bacterial proteins, other than L514S, L552S, or XAGE-1. These data clearly demonstrate that both molecularly defined CT antigens L514S and L552S are immunogenic, at least in terms of humoral responses, suggesting that both CT antigens are promising candidates for immunotherapy.
Department of Immunology, Antigen Discovery of Corixa Corporation, Seattle, WA 98104, USA. yoshihiro.watanabe@ims.jti.co.jp
Yoshihiro
Y
Watanabe
Stephen
S
LePage
Mark
M
Elliott
Heather
H
Secrist
Takao
T
Tanaka
Masaaki
M
Kawahara
Akihide
A
Matsumura
Shigeto
S
Hosoe
Mitsumasa
M
Ogawara
Masaji
M
Okada
Betsey
B
Repasky
Paul
P
Sleath
Tongtong
T
Wang
Robert
R
Henderson
D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008969:Molecular Sequence Data; D012333:RNA, Messenger; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000276:immunology*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C413656:XAGE1A protein, human