Identification of new tumor antigens using testis-specific proteins

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10670175
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Keio University
• Principal Investigator: FUJITA Tomonobu Keio University, School of Medicine, Instructor, 医学部, 助手 (20199334)
• Co-Investigator(Kenkyū-buntansha): HATA Junichi Keio University, School of Medicine, Professor, 医学部, 教授 (90051614) ; IKEDA Hideyuki Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (40301494) ; KAWAKAMI Yutaka Keio University, School of Medicine, Professor, 医学部, 教授 (50161287) ; MURAI Masaru Keio University, School of Medicine, Professor, 医学部, 教授 (90101956)
• Project Period (FY): 1998 – 1999
• Keywords: CT antigen / SAGE / SEREX

Research Abstract

Cancer-Testis (CT) antigens that are expressed in normal testis and various tumors are promising targets for immunotherapy for cancer. To identify new CT antigens, we used 2 strategies: Isolation of testis specific genes that also express in tumor cells, and screening of a testis cDNA library with sera from cancer patients. Profile of mRNA of testis was analyzed using SAGE (serial analysis of gene expression), and approximately 20,000 tags containing 12,400 tags for distinct proteins were identified in the testis SAGE library. By comparing it with SAGE databases from selected other normal and cancer tissues, we have obtained candidate tags for new CT antigens. However, more detained analysis of these selected tags revealed that genes containing these tags with high expression were not specific for testis and cancer. Thus, new CT was not identified among these selected genes. Further analysis of selected tags with relatively low expression remains to be performed. The testis cDNA library was screened with sera from 2 pancreatic cancer patients and a bladder cancer patient, and 5 positive clones were obtained. CT-1 isolated with the pancreatic cancer patient's serum was a novel gene not registered in the gene database. IgG antibodies for CT-1 was detected in 1 of 5 sera from pancreatic cancer patients and 1 of 10 sera with renal cancer patients, but was not detected in 20 sera from healthy individuals. CT-1 was expressed in only testis among normal tissues tested and in 1 of 15 pancreatic cancer cell lines and 2 of 5 pancreatic cancer tissues. These results demonstrated that CT-1 was a new CT antigen expressed in some pancreatic cancers.