| Project/Area Number |
03670640
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | OSAKA CITY UNIVERSITY |
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Principal Investigator |
CHUNG Yong-Suk Osaka City Univ. Med.Sch. 1st.Dep.of Surgery, assistant Prof., 医学部, 講師 (40188652)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Pancreatic caner / Nd2. / Chimeric Nd2 / Targeting therapy / Radioimmunodetection / Monoclonal antibody / ミサイル治療 |
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| Research Abstract |
New strategy in diagnosis and treatment for pancreatic cancer utilizing monoclonal antibody.
1. Radioimmunodetection in pancreatic cancer
ND2 is a murine monoclonal antibody produced against a mucin fraction purified from pancreatic cancer cell line SW1990 and the antigen recognized has been clarified to be a non circulating antigen. Distinct immunoscintig rams of corresponding tumors in patients with pancreatic cancer were obtained by administration of 111In-Nd2 and positive rate of Radioimmunodetection was 62.5% with no false positives which indicated 100% specificity.
Targeting therapy of pancreatic cancer in nude mice model.
Human pancreatic cancer cell line SW1990 was employed as a xenograft in athymic nude mice to evaluate the effect of targeting therapy with 131I-Nd2 and Adriamycin conjugated Nd2. Both 131I-Nd2 and ADM-Nd2 specifically supressed the growth of established tumors in vivo and prolonged the life span of tumor bearing nude mice compared to control groups. Radiolabeled and ADM conjugated Nd2 would provide therapeutic effects in pancreatic cancer.
Preparation of chimeric Nd2
Nd2 has showed promising results of Radioimmunodetection and Targeting therapy in pancreatic cancer. However, murine monoclonal antibody may lead to an appearance of HAMA (human anti mouse antibody) which is a serious problem in the repeated administration for clinical use. Therefore, mouse-human chimeric antibody are expected to be reduced antigenicity. The chimeric Nd2 consisting of mouse derived variable regions and human derived constant regions was shown to bind mucins purified from SW1990 with same dose response curve as murine Nd2. Immunohistochemical study showed that chimeric Nd2 has same specificity for pancreatic cancer tissues as murine Nd2. The chimeric Nd2 looks promising for clinical application.
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