The synovial membrane, liver, and tongue: target organs for a ricin A-chain immunotoxin (ZD0490).

ABSTRACT

ZD0490 is an immunotoxin consisting of a mouse monoclonal antibody conjugated to recombinant ricin A-chain (rRAC). It was developed at Zeneca Pharmaceuticals as a treatment for certain antigen-bearing tumors. During safety evaluation studies in rats, a number of reversible inflammatory changes were seen. The synovial membranes of articular joints showed a marked degeneration and necrosis with an associated inflammation. When of mild severity only the synovial membrane was involved, but when more severe many adjacent tissues including the surface of the articular cartilage were affected. Some nonspecific skeletal muscle toxicity occurred. However, tongues from the intravenously (tail) dosed rats consistently showed inflammation specifically located in the ventral subepithelial area with myocyte degeneration and necrosis. Also, hepatic peliosis primarily located in the subcapsular areas was induced. Studies with rRAC alone indicated that ricin A-chain (RAC) is the component responsible for these findings. It is suggested that cells of a macrophage type with the ability to specifically bind RAC may at least in part determine the location and nature of the changes seen.