Preparation of a conjugate of mitomycin C and anti-neural cell adhesion molecule monoclonal antibody for specific chemotherapy against biliary tract carcinoma.
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.
Tanaka
J
J
Department of Surgery, Akita University School of Medicine, Japan.
Sato
E
E
Saito
Y
Y
Kusano
T
T
Koyama
K
K
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology* / Q000378:metabolism; D003488:Cyanogen Bromide; D006801:Humans; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000627:therapeutic use*; D016685:Mitomycin / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D000922:Immunotoxins; D016685:Mitomycin; D003488:Cyanogen Bromide