THE SYNOVIAL-MEMBRANE, LIVER, AND TONGUE - TARGET ORGANS FOR A RICIN A-CHAIN IMMUNOTOXIN (ZD0490)

ZD0490 is an immunotoxin consisting of a mouse monoclonal antibody con jugated to recombinant ricin A-chain (rRAC). It was developed at Zenec a Pharmaceuticals as a treatment for certain antigen-bearing tumors. D uring safety evaluation studies in rats, a number of reversible inflam matory changes were seen. The synovial membranes of articular joints s howed a marked degeneration and necrosis with an associated inflammati on. When of mild severity only the synovial membrane was involved but when more severe many adjacent tissues including the surface of the ar ticular cartilage were affected. Some nonspecific skeletal muscle toxi city occurred. However, tongues from the intravenously (tail) dosed ra ts consistently showed inflammation specifically located in the ventra l subepithelial area with myocyte degeneration and necrosis. Also, hep atic peliosis primarily located in the subcapsular areas was induced. Studies with rRAC alone indicated that ricin A-chain (RAC) is the comp onent 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.