| Co-Investigator(Kenkyū-buntansha) |
MATSUZAKI Yuriko Keio University, School of medicine, Instructor, 医学部, 助手 (40255435)
KAWAKAMI Yutaka Keio University, School of medicine, Professor, 医学部, 教授 (50161287)
AOKI Daisuke Keio University, School of medicine, Professor, 医学部, 教授 (30167788)
野澤 志朗 慶應義塾大学, 医学部, 教授 (90051557)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
In this study, using new various immunological methods, we identified a novel cancer-antigen which is useful not only for an immune therapy target but also a biomarker for the diagnosis of adenocarcinoma in the uterine cervix. We obtained 19 tumor tissue samples and 29 blood samples from cervical cancer patients at operation. We determined the presence of HPV infection of these tissues and the HPV type by HPV-E7 specific PCR and sequencing. In squamous cell carcinoma 8 cases, we detected 4 cases of HPV 16-related type (16,31,58) and 1 case of HPV 18-related type (39). In 9 adenocarcinoma cases, we detected 4 cases of HPV 18-type and 2 cases of HPV 16-type. From 13 cervical cancer samples, we transplanted the cancer tissue into SCID mice. After detecting human IgG in these SCID mice from tumor-infiltrating B lymphocytes, we harvested the sera. We constructed lambda phage cDNA expression libraries from cervical cancer cell lines, SKG-II/SKG-IIIb, TCO-1, Hela. In addition, we constructed
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lambda phage cDNA expression libraries from 4 cases of cancer tissues. First, we screened TOC-1 library with the sera from tumor transplanted SCID mice. In the case of HPV-18 positive adenocarcinoma, NY-REN-58, reported as candidate of cancer antigen in renal cancer, was identified from these sera using this method. Tumor rejection antigen-1 (gp96) was reported to be a molecular chaperon of antigen presenting cells, and studied for peptide vaccine therapy application because of its association with tumor immunity. Then, transplanted the metastatic tissue separately from primary tissue of HPV 18 positive cervical adenocarcinoma, we screened SKG-II/IIIb library with two sera from primary and metastatic. We isolated 500,000 cDNA clones, but a positive clone was not determined. Then we isolated over 400 positive clones using a testis library from each screening, and we are currently continuing the investigation of these positive clones. We will screen other libraries from HPV 18-positive cancer tissue or HPV 16-positive cancer tissue with the sera of tumor-planted SCID mice and identify a cancer antigen for clinical diagnosis and treatment of cervical adenocarcinoma. Less
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