Method of killing B-cells in a complement independent and an ADC

Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Binds specifically-identified oligosaccharide structure

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4241401, 4241421, 4241521, 4241411, 4241561, 4241741, 4352401, A61K 39395

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active

054179726

ABSTRACT:
Methods are provided for inducing cell death in B-cells, including neoplastic B-cells, by employing reagents that bind to a B-cell epitope. Particularly, antibodies specific for the marker can be administered to a host to induce death in B-cells to which the antibodies bind or can be used in ex vivo clinical situations to selectively remove B-cells. A B-cell specific oligosaccharide epitope useful as a B-cell marker has been identified. The ligand being recognized on B lymphocytes has no apparent similarities to any of the known pan-B cells markers. In addition, proteins which specifically bind the disclosed epitope are provided. Human monoclonal antibody 216, which recognizes this B-cell epitope, is cytotoxic to B-cells and binds all CD19.sup.+ and CD20.sup.+ B lymphocytes in human peripheral blood and spleen. Furthermore, MAb 216 does not distinguish B cells by the isotype expressed, binding IgG.sup.+ and IgM.sup.+ cells with equal intensity, and also bind all B cells regardless of their CD5 expression. Methods to inhibit neoplastic B-cell growth by administering a B-cell-cytotoxic protein are presented. These products and methods find use in diagnosis and therapy.

REFERENCES:
Grillot-Courvalin, Catherine et al., "An anti-B cell autoantibody from Wiskott-Aldrich syndrome which recognizes i blood group specificity on normal human B cells," Eur. J. Immunol. (1992) 22:1781-88.
Teng et al., PNAS, 82:1790, 1985.
Bhat et al., J. Immunol., 151:5011, 1993.
Osband et al., Immunol. Today, 11:193, 1990.
Harris et al., Tibtech, 11:42, 1993.

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