The selection of monoclonal antibodies for tumour localization in patients with colorectal carcinoma

Abstract

We have investigated the ability of various predictive studies to assess which monoclonal antibody (MCA) will be most useful in the immunoscintigraphic localization of metastatic colorectal carcinoma. A set of MCAs was obtained by fusing splenic lymphocytes from rats immunized with membrane preparations from fresh human colorectal cancer. Supernatants from 17 cloned hybridomas were found to bind strongly to colon carcinoma lines by indirect radioimmunoassay. Immunofluorescence using these MCAs on sections of fresh frozen colon carcinoma and normal tissue revealed different staining patterns. Nine MCAs were purified and labelled with 131I. Groups of mice bearing human colorectal tumour xenografts were given radiolabelled MCA and scanned. Six out of the nine MCAs showed tumour localization as determined by rectilinear scanning. Three MCAs which gave good tumour images in mice were selected for clinical evaluation in patients with advanced colorectal cancer. One gave good tumour images, another targeted to bone marrow and the third bound almost exclusively to normal liver. Clinical evaluation is clearly essential in the selection of MCAs for tumour localization.