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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2562-2568
A Bispecific Diabody That Mediates Natural Killer Cell Cytotoxicity
Against Xenotransplantated Human Hodgkin's Tumors
Michaela A.E. Arndt,
Jürgen Krauss,
Sergey M. Kipriyanov,
Michael Pfreundschuh, and
Melvyn Little
From the Recombinant Antibody Research Group (D0500), German Cancer
Research Center (DKFZ), Heidelberg, Germany; and the Department of
Internal Medicine I, University Clinic of Saarland, Homburg, Germany.
CD16/CD30 bispecific monoclonal antibodies can induce remissions of
Hodgkin's disease refractory to chemo- and radiotherapy. However, the
development of human antimouse immunoglobulin antibodies and allergic
reactions precludes repeated applications of the antibody. Moreover,
problems of producing and purifying sufficient amounts of material
limit the clinical practicability of this novel treatment approach. To
overcome these obstacles, we have constructed a bispecific antibody in
a diabody form that only employs the variable domains of the CD16/CD30
hybrid hybridoma. The diabody compared favorably with the parent
CD16/CD30 bispecific antibody in its ability to activate and target
natural killer cells in vitro. Its administration to mice bearing
xenografted Hodgkin's lymphoma resulted in a marked regression of
tumor 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 refractory Hodgkin's lymphoma.
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