Immunoscreening of a cDNA library from a lung cancer cell line using autologous patient serum: Identification of XAGE‐1b as a dominant antigen and its immunogenicity in lung adenocarcinoma

• Published in: International journal of cancer Vol. 108; no. 4; pp. 558 - 563
• Main Authors: Ali Eldib, Ali Mohamed, Ono, Toshiro, Shimono, Michihide, Kaneko, Miho, Nakagawa, Kazuhiko, Tanaka, Ryo, Noguchi, Yuji, Nakayama, Eiichi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 10.02.2004
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - genetics; Adenocarcinoma - immunology; Adult; Alternative Splicing; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; cancer/testis antigen; Cloning, Molecular; Gene Expression Regulation, Neoplastic; Gene Library; Humans; Immunodominant Epitopes - immunology; lung adenocarcinoma; Lung Neoplasms - blood; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Male; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Sequence Analysis, DNA; SEREX; Tumor Cells, Cultured; XAGE‐1
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11587

By serologic identification of antigens by recombinant expression cloning (SEREX) analysis using an autologous lung adenocarcinoma cell line, OU‐LU‐6, as a cDNA library source, we demonstrated that XAGE‐1 was the dominant antigen recognized by serum from a patient. By immunoscreening, we obtained 38 positive cDNA clones consisting of 16 genes designated as OY‐LC‐1 to ‐OY‐LC‐16. OY‐LC‐1, represented by 18 clones, was identical to XAGE‐1. OY‐LC‐2 to ‐16, represented by either a single or 2 clones, were identical to known genes shown to be ubiquitously expressed in various normal tissues. RT‐PCR analysis showed that of 4 XAGE‐1 transcripts—XAGE‐1a, b, c and d—XAGE‐1b was expressed in OU‐LU‐6 dominantly. Furthermore, XAGE‐1b mRNA was expressed in 4 of 10 lung cancer tissues, whereas no expression was observed in normal tissues. Of 4 XAGE‐1b mRNA positive cancer tissues, 3 were adenocarcinoma and one was poorly differentiated squamous cell carcinoma. Of 32 sera from lung cancer patients, 8 sera were reactive with the XAGE‐1b product. Those 8 sera were from patients with adenocarcinoma. These findings indicated strong immunogenicity of XAGE‐1b in lung adenocarcinoma and suggested its potential use as a target for vaccine‐based immunotherapies. © 2003 Wiley‐Liss, Inc.