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Cytolysis of leukemic B-cells by T-cells activated via 2 bispecific antibodies

Item Type:Article
Title:Cytolysis of leukemic B-cells by T-cells activated via 2 bispecific antibodies
Creators Name:Bohlen, H. and Manzke, O. and Patel, B. and Moldenhauer, G. and Doerken, B. and von Fliedner, V. and Diehl, V. and Tesch, H.
Abstract:Bispecific monoclonal antibodies can be used in the activation of effector cells to lyse autologous tumor cells. We analyzed the activation of human T-cells in vitro with bispecific monoclonal antibodies, which were generated by hybridoma-hybridoma fusion. Preactivated allogeneic and autologous T-cells could be triggered to lyse tumoral B-cells in the presence of CD3 x CD19 bispecific antibodies. In addition, the combined use of two CD3 x CD19 plus CD28 x CD22 bispecific antibodies induced optimal interleukin 2 secretion by Jurkat T-cell acute lymphocytic leukemia cells in the presence of target B-cells. The same antibody combination was able to generate cytolytic effector cells without prior activation, when resting T-cells were cocultured with freshly isolated autologous leukemic B-cells in the presence of the bispecific antibodies. The results suggest that signals required to activate cytolytic T-cell precursors can be provided by the two bispecific antibodies. Although activation of resting T-cells can be achieved by CD3 x CD19 bispecific antibodies in association with monospecific bivalent CD28 antibodies, the second bispecific antibody, CD28 x CD22, further increases the specificity of the target cell dependent activation of T-cells. When used for immunotherapy of B-cell malignancies, the CD3 x CD19 and CD28 x CD22 bispecific antibody combination may avoid the need for ex vivo activated effector cells, because the antibodies may induce T-cell activation directly at the tumor site.
Keywords:Monoclonal Antibodies, Antibody Specificity, CD Antigens, B-Lymphocyte Differentiation Antigens, T-Lymphocyte Differentiation Antigens, Cell Adhesion Molecules, Immunologic Cytotoxicity, Lectins, B-Cell Leukemia, Lymphocyte Activation, Cytotoxic T-Lymphocytes, Cultured Tumor Cells, Animals, Mice
Source:Cancer Research
ISSN:0008-5472
Publisher:American Association for Cancer Research (U.S.A.)
Volume:53
Number:18
Page Range:4310-4314
Date:15 September 1993
Official Publication:http://cancerres.aacrjournals.org/content/53/18/4310.abstract
PubMed:View item in PubMed

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