Therapy with CD7 monoclonal antibody TH-69 is highly effective for xenografted human T-cell ALL |
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Authors: | Wolfgang,Baum ,Helmuth,Steininger ,Hans-Jü rgen, Bair ,Wolfgang,Becker ,Thomas E.,Hansen-Hagge ,Michael,Kressel ,Elisabeth,Kremmer ,Joachim R.,Kalden & Martin,Gramatzki |
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Affiliation: | Division of Haematology/Oncology, Department of Medicine III;, Institute of Pathology;, Department of Nuclear Medicine, University of Erlangen-Nu¨rnberg, Erlangen;, Department of Pediatrics, University of Ulm, Ulm;, Institute of Immunology, GSF, Mu¨nchen, Germany;, Institute of Anatomy, University of Zu¨rich, Zürich, Switzerland |
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Abstract: | Human T-cell acute lymphocytic leukaemia (ALL) was established in athymic nude or severe combined immunodeficient (SCID) mice by injecting CEM or MOLT-16 cells. When nude mice bearing approx. 2 g of tumour were treated with a single injection of CD7 antibody TH-69, 82.6% reached complete remission within 10 d whereas 13.0% showed partial remission. Similarly, in SCID mice with advanced disease a significant prolongation of survival was seen. The therapeutic effects were dependent upon dose and affinity of the antibody. TH-69 is a high-affinity antibody (7.6 × 109 M −1) that rapidly induced modulation during treatment. The Fc-portion of the antibody was required for effective tumour cell killing. Complement deposition was found on tumour sections after TH-69 treatment and in part may account for tumour destruction. There was no evidence for antibody-dependent cellular cytotoxicity (ADCC). The kinetics of tumour disappearance suggested the initiation of a programmed cell death (PCD), despite the lack of significant DNA fragmentation. Unmodified high-affinity antibodies to the T-cell antigen CD7 have potential for T-cell ALL therapy. |
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Keywords: | T-cell ALL human xenograft CD7 monoclonal antibody therapy |
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