Development of monoclonal antibodies against human gastrointestinal cancer.

Abstract

We have evaluated approximately 10,000 monoclonal antibodies resulting from 14 hybridization of spleen cells from mice immunized with established cancer cell lines. They were screened by binding assays using cancer cell lines or normal fibroblast cells, followed by immunohistochemical study on tissue sections. Ninety-one monoclonal antibodies were obtained by above binding assays. One of them, named KM10 was further investigated. Isotype of KM10 was IgGI with x-light chain. It was shown that KM10 has strong reactivity with tumors of colon, stomach, papilla Vater, and pancreas, while the limited reactivity displayed with normal tissues. The electron microscopic observation revealed that the antigen recognized by KM10 is expressed on the surface of cancer cells. KM10 could mediate ADCC. These results indicate that KM10 is a good candidate for a probe of diagnosis and therapy of cancer. monoclonal antibody ; gastrointestinal cancer Monoclonal antibodies have provided a new powerful approach to diagnosis and therapy of cancer. Because monoclonal antibody is derived from an antibody producing cell clone, it is homogenous with respect to its subclass and specificity, and demonstrates specific binding to unique epitopes. Many monoclonal antibodies against malignant cells have been made (Edwin and Sikora 1982;Marx 1982; Damj anov and Knowles 1983;Abrams and Oldham 1985).

Selection of monoclonal antibodies detecting KM01 antigen.

“…We also have been developing new MoAbs useful for the diagnosis and therapy of cancer (Ohyanagi et al 1988; Kano et al 1990a), some of which were found to be cross-reactive with KMO1. They were divided into three groups depending on their reactivity with glycolipid antigens isolated from COLO-201.…”

“…Murine MoAb KMO1, AF6, BF2, B03, CE5, FD5, HH9, 1E3, and JG2 were developed in our laboratories using cancer cell lines as the immunogen (Ohyanagi et al 1987 ; Kano et al 1990a). Anti-hepatitis B surface (HBs) antigen monoclonal antibody 2117 (IgM), the negative control antibody was also developed in our laboratories.…”