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BK Link and GJ Weiner
Department of Internal Medicine, University of Iowa College of Medicine,
Iowa City.
Bispecific monoclonal antibodies (bsabs) recognizing both CD3 and a tumor
antigen can redirect T-cell-mediated cytotoxicity toward cells bearing that
antigen. Such bsabs have been shown to be more effective than monospecific
monoclonal antibodies (MoAbs) at preventing tumor growth in animal models
of B-cell malignancy. The current studies describe the production and
preliminary evaluation of a bsab designed to induce the lysis of malignant
human B cells by human T cells. The bsab was obtained from a
hybrid-hybridoma cell line produced by fusing OKT3-secreting hybridoma
cells with hybridoma cells that secrete 1D10. 1D10 is an MoAb that
recognizes an antigen found on a majority of malignant human B cells that
has not been detected to a significant degree on normal resting or
activated lymphocytes. High performance liquid chromatography (HPLC) was
used to separate bsab from monospecific antibodies that were also present
in the hybrid-hybridoma antibody product. The bsab was then evaluated in
vitro for its ability to induce lysis of malignant B cells by activated T
cells. The bsab consistently induced extensive lysis in vitro of 1D10 (+)
cells, including both cell lines and cells obtained from patients with a
variety of B-cell malignancies. No such effect was seen with activated T
cells alone or activated T cells with monospecific antibody. No increased
lysis was seen with 1D10 (-) cell lines. The bsab also mediated lysis of
malignant B cells by autologous T cells. We conclude bsab containing an
OKT3 arm and a 1D10 arm can induce T-cell-mediated lysis in a manner that
is both potent and specific. This supports further evaluation of this bsab
as a potential immunotherapy of B-cell malignancy.
This article has been cited by other articles:
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| Copyright © 1993 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||