Preparation of a conjugate of mitomycin C and anti-neural cell adhesion molecule monoclonal antibody for specific chemotherapy against biliary tract carcinoma.

Abstract

To develop a specific chemotherapy modality for the perineural invasion of neural cell adhesion molecule (NCAM) positive biliary tract cancer, an anticancer drug, mitomycin C (MMC), was covalently bound to anti-NCAM monoclonal antibody (anti-NCAM MoAb) to form a conjugate using the cyanogen bromide method. The substitution ratio of the conjugate determined spectrophotometrically was 3.5 (MMC mol/immunoglobulin G mol). The cytotoxic activity of the conjugate, which was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test in the growth inhibition of the neuroblastoma cell line with NCAM expression, was maintained at 65.8% to 94.5% compared with the same concentration of MMC solution. The binding activity of the conjugate to the NCAM-positive bile duct cancer was examined by immunohistochemical staining and proved to be the same level as that of free anti-NCAM MoAb. The conjugate prepared in this study therefore appeared to be a potentially useful tool for immunotargeting specific chemotherapy against biliary tract cancer with NCAM expression.

• Authors: J Tanaka, E Sato, Y Saito, T Kusano, K Koyama
• Journal: Surgery today (Surg Today) Vol. 28 Issue 11 Pg. 1217-20 ( 1998) ISSN: 0941-1291 [Print] Japan
• PMID: 9851639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Antibodies, Monoclonal
• Cell Adhesion Molecules, Neuronal
• Immunotoxins
• Mitomycin
• Cyanogen Bromide

Topics

• Antibiotics, Antineoplastic (therapeutic use)
• Antibodies, Monoclonal
• Biliary Tract Neoplasms (drug therapy, metabolism)
• Cell Adhesion Molecules, Neuronal (immunology, metabolism)
• Cyanogen Bromide
• Humans
• Immunohistochemistry
• Immunotoxins (therapeutic use)
• Mitomycin (therapeutic use)