Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Specific chemotherapy with conjugate of anticancer drug and anti-neural cell adhesion@molecule antibody against perineural invasion of pancreato-biliary tract cancer

J Tanaka MD 1, T Kusano MD, Y Saito MD 2, T Yoshioka MD, K Koyama MD

1 Div Surgery, Akita City Hospital,, 2 Dept Surgery, Akita University School of Medicine, Japan,

AIM: Perineural invasion is one of the most important prognostic factors in pancreato-biliary tract cancer, and recent reports indicate a close relationship between expression of neural cell adhesion molecule (NCAM) and cancer infiltration into the perineural space. To develop specific chemotherapy for perineural invasion, conjugate of anticancer drug and monoclonal antibody was prepared and evaluated anticancer activity and antibody activity of the conjugate in vitro. Materials and Methods: Mitomycin C (MMC) and anti-NCAM antibody conjugate was prepared with cyanogen bromide (BrCN) method. The degree of substitution was determined spectrophotometrically. A drug activity of conjugate was tested by MTT method of the growth inhibition with neuroblastoma cell line (IMR-32). Antibody activity of conjugate was examined by immunohistochemical staining with Avidin-Biotinylated enzyme complex on NCAM positive bile duct cancer. RESULTS: Average degree of substitution in conjugate was 3.5 (mol concentration of drug / mol concentration of antibody). A drug activity of conjugate was maintained 66 to 95 % compared with same concentration of MMC solution. Antibody activity of conjugate showed the same level as that of antibody alone. CONLUSION: MMC could be linked to anti-NCAM monoclonal antibody with BrCN method. The conjugate has both anticancer activity and antibody activity, therefore it can be useful for specific targeting chemotherapy in pancreato-biliary tract cancer.

KEY WORDS: conjugate, neural cell adhesion molecule, specific chemotherapy.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on synergistic therapies.