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 antimouse immunoglobulin antibodies and allergic reactions precludes repeated applications of the antibody. Moreover, problems of produc...

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Bibliographic Details
Published in:Blood 1999-10, Vol.94 (8), p.2562-2568
Main Authors: ARNDT, M. A. E, KRAUSS, J, KIPRIYANOV, S. M, PFREUNDSCHUH, M, LITTLE, M
Format: Article
Language:English
Subjects:
Animals
Antibodies, Bispecific - immunology
Antibodies, Bispecific - therapeutic use
Antigens, CD20 - immunology
Antineoplastic agents
Biological and medical sciences
Cytotoxicity, Immunologic
Drug Screening Assays, Antitumor
Female
Hodgkin Disease - immunology
Hodgkin Disease - therapy
Humans
Hybridomas - immunology
Immunization, Passive
Immunoglobulin Variable Region - immunology
Immunoglobulin Variable Region - therapeutic use
Immunotherapy
Killer Cells, Natural - immunology
Medical sciences
Mice
Mice, Inbred BALB C
Mice, SCID
Neoplasm Transplantation
Pharmacology. Drug treatments
Receptors, IgG - immunology
Specific Pathogen-Free Organisms
Transplantation, Heterologous
Tumor Cells, Cultured - immunology
Tumor Cells, Cultured - transplantation
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Description
Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V94.8.2562.420k20_2562_2568