Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumour cells

Publisher Website
Google Scholar
Abstract
Several attempts to attack tumors in experimental systems have been made using conjugates of chemotherapeutic agents or potent toxins with antibodies (immunotoxins). In vitro studies have been highly successful, showing target specificity of a high order in some cases. So far, such conjugates have been inadequate in vivo, probably for 2 main reasons. First, conventional heteroclonal antibodies are perhaps inappropriate, because purification by biochemical methods leaves a large amount of non-antibody .gamma.-globulins. The use of monoclonal antibodies may overcome this problem. Second, when whole toxins have been conjugated to antibodies there has been a strong residual nonspecific cytotoxicity due to the binding capacity of a subunit, the B-piece of the toxin. (Diphtheria toxin or ricin consist of 2 polypeptide subunits. The A-piece is responsible for inhibition of protein synthesis on ribosomes; the B-piece binds to galactose residues on the cell membrane and facilitates the transmembrane passage of the A-piece.) The problem of nonspecific binding by the B-piece was circumvented by using the A-piece only as the toxin component of immunotoxins; these immunotoxins are active in vitro and in vivo. [The monoclonal IgM antibody used was directed against the Thy 1.2 antigen of mouse T cells. Mouse leukemia WEHI-7 cells, bearing the Thy 1.2 antigen, were used as target cells for the immunotoxins.].