1995 Fiscal Year Final Research Report Summary
Specific chemothrapy for perineural invasion of biliary tract cancer with conjugate of anticancer drug and anti-neural cell adhesion molecule antibody
| Project/Area Number |
06671240
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| 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) |
SATO Yasuhiko Akita University, Surgery, Research associate, 医学部, 助手 (80235407)
KOTANAGI Hitoshi Akita University, Surgery, Research associate, 医学部, 助手 (00161935)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Keywords | biliary tract cancer / perineural invasion / neural cell adhesion molecule / anticancer drug-monoclonal antibody conjugate |
|---|
| Research Abstract |
Conjugate of chemotherapeutic drug (Mitomycin C,MMC) and monoclonal antibody, which was anti-Neural cell adhesion molecule (NCAM) antibody was prepared and evaluated anticancer activity and antibody activity of the conjugate in vitro. MMC and anti-NCAM antibody conjugate was prepared according to Suzuki et al with cyanogen bromide (BrCN) method.
The degree of substitution was determined spectrophotometrically by assuming that MMC has absorbance with lambdamax=363nm, E1%1cm=623 and IgG has absorbance with lambda max=280nm, E1%/1cm=13.5. The degree of substitution which was calculated as follows : degree of substitution=mol concentration of drug contained in conjugate/mol concentration of antibody contained in conjugate, was 3.5 (average).
A drug activity of conjugate, which was tested by MTT method of the growth inhibition with neuroblastoma cell line (IMR-32) was maintained 66 to 95% compared with same concentration of MMC solution.
Antibody activity of conjugate, which was examined by immunohistochemical staining with Avidin-Biotinylated enzyme Complex on NCAM positive bile duct cancer, showed the same level as that of antibody alone.
In conclusion, MMC could be linked to anti-NCAM monoclonal antibody by BrCN method. Since this conjugate has both activity of drug and antibody, it can provide an useful tool for specific targeting cancer chemotherapy.
|
