A bispecific diabody that mediates natural killer cell cytotoxicity against xenotransplantated human Hodgkin's tumors

CD16/CD30 bispecific monoclonal antibodies can induce remissions of Hodgkin 's disease refractory to chemo- and radiotherapy. However, the development of human anti-mouse immunoglobulin antibodies and allergic reactions preclu des repeated applications of the antibody. Moreover, problems of producing and purifying sufficient amounts of material limit the clinical practicabil ity of this novel treatment approach. To overcome these obstacles, we have constructed a bispecific antibody in a diabody form that only employs the v ariable domains of the CD16/CD30 hybrid hybridoma, The diabody compared fav orably with the parent CD16/CD30 bispecific antibody in its ability to acti vate and target natural killer cells in vitro. Its administration to mice b earing xenografted Hodgkin's lymphoma resulted in a marked regression of tu mor growth, thus proving for the first time the capability of a diabody for immune recruitment in vivo. The CD16/CD30 diabody is a novel reagent that should considerably facilitate the immunotherapy of patients with refractor y Hodgkin's lymphoma. (C) 1999 by The American Society of Hematology.