Specific chemotherapy for pancreato-biliary tract cancer with conjugate of anti-neural cell adhesion molecule antibody and anticancer drug

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671409
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: AKITA UNIVERSITY
• Principal Investigator: TANAKA Jun-ichi Akita University, Surgery, Research Associate, 医学部, 助手 (30171763)
• Co-Investigator(Kenkyū-buntansha): KOTANAGI Hitoshi Akita University, Surgery, Lecturer, 医学部, 講師 (00161935) ; ASANUMA Yoshihiro Akita University, Surgery, Assistant Professor, 医学部, 助教授 (20142937)
• Project Period (FY): 1996 – 1997
• Keywords: Pancreato-biliary tract cancer / perineural invasion / neural cell adhesion molecule / anticancer drug-monoclonal antibody conjugate

Research Abstract

The aim of this study was to develope a specific chemotherapy modality for the perineural invasion of neural cell adhesion molecule (NCAM) positive pancreato-biliary tract cancer. An anti-cancer drug Mitomycin C (MMC) was covalently bound to anti-NCAM monoclonal antibody (MoAb) to form a conjugate using a cyanogen bromide method. The cytotoxic activity of the conjugate was maintained at 66 to 95% compared with the same concentration of MMC solution. The binding activity of the conjugate to the NCAM positive bile duct cancer was proved to be the same level as that of tree 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.
To investigate the distribution and the anticancer activity of the conjugate to the tumor, NCAM expression was examined with immunohistochemical staining for human cancers, cholangiocellular carcinoma (CCC-1, CCC-2) and bile duct carcinoma (TGGK,GGK) in tumor bearing nude mice. However, NCAM expression was not detected. Expression of NCAM antigen was studied with flow-cytometry by using anti-NCAM MoAb following anit-mouse immunoglobulin G (IgG) antibody coupled with FITC.No significant level of NCAM expression was revealed in several human cancer cell lines including HUCCT1, HUH28 (cholangiocellular carcinoma), PK-1, PK-9 (pancreatic cancer) and CaR-1, RCM-1 (rectal cancer).
To proceed this study, stable NCAM positive cancer cell line should be established with transfection of NCAM cDNA into human pancreato-biliary tract cancer cell line.