Cytolysis of leukemic B-cells by T-cells activated via two bispecific antibodies.
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.
Bohlen
H
H
Universität zu Köln, Klinik I für Innere Medizin, Germany.
Manzke
O
O
Patel
B
B
Moldenhauer
G
G
Dörken
B
B
von Fliedner
V
V
Diehl
V
V
Tesch
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018106:CD28 Antigens; D017252:CD3 Complex / Q000276:immunology; D015815:Cell Adhesion Molecules; D003602:Cytotoxicity, Immunologic; D006801:Humans; D037102:Lectins; D015448:Leukemia, B-Cell / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D051918:Sialic Acid Binding Ig-like Lectin 2; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; C497867:CD22 protein, human; D018106:CD28 Antigens; D017252:CD3 Complex; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2