Preparation of cytotoxic antibody-toxin conjugates

Conjugates of antibodies with plant toxins, such as ricin and abrin, are potent cytotoxic agents that selectively eliminate target cells from mixed cell cultures in vitro, and have great promise as antitumor agents in cancer therapy (1). Ricin and abrin are protein toxins consisting of two different polypeptide subunits, the A and B chains, which are of similar size (between 30 and 34 kDa) and are joined by a single disulfide bond. The A chain is a ribosome-inactivating protein (RIP) that inactivates eukaryotic ribosomes by a specific irreversible covalent modification of the ribosomal RNA (2). The B chain binds to cell surface galactose-containing oligosaccharide residues. Following receptor-mediated endocytosis of toxin bound to the cell surface, the A chain gains access to the cytosol and destroys the ability of the cell to make protein (3).