| Project/Area Number |
06671253
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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 | Niigata University |
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Principal Investigator |
NISHIMAKI Tadashi Niigata University School of Medicine, Department of Surgery, Instructor, 医学部・附属病院, 助手 (70242427)
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| Co-Investigator(Kenkyū-buntansha) |
OKA Yoshiaki Niigata University School of Medicine, Department of Surgery, Medical Staff, 医学部・附属病院, 医員
AIZAWA Kikuo Niigata University School of Medicine, Department of Surgery, Instructor, 医学部・附属病院, 助手 (10222449)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | monoclonal antibody / adriamycin / immuno conjugate / target therapy / placental alkaline phosphatase / MTT assay / モノクローナル抗体 / タゲット療法 |
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| Research Abstract |
We performed a fundamental in-vitro study to test whether augmentation of anti-tumor effect of immuno-targeting therapy for gastrointestinal carcinoma is induced by increasing tumor-antigen expression.
Anti-placental alkaline phosphatase (PLAP) mouse-monoclonal antibody (M1H2) was obtained with a hybridoma method using a human gastric cancer cell line (MKN1) expressing PLAP antigen. M1H2 belonged to IgM subclass. After deoxidization of M1H2, half-monomeric IgM M1H2 was conjugated with adriamycin. This M1H2-adriamycin immunocomplex showed a specific reaction to PLAP expressing tumor cell lines (MKN1 and MKN7). However, the immunotiter of M1H2-adriamycin complex was reduced 1/4-1/8 when compared with the titer of half-monomeric M1H2 alone. It was revealed by MTT-assay that IC50 of adriamycin and M1H2-adriamycin immunomcoplex was 0.20mug/ml and 0.19mug/ml for MKN1, respectively ; 0.27mug/ml and 0.30mug/ml for MKN7, respectively. These results indicated that anti-tumor effect of the M1H2-adriamycin complex was not superior to that of adriamycine alone.
Even after an augmentation of PLAP antigenicity by hydrocortisone treatment, increased anti-tumor effect of the M1H2-adriamycin complex was not observed.
Decreased binding activity of the M1H2-adriamycin complex to the tumor cells was considered to be a reason of the negative results and further studies are needed.
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