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Teiluf, K.* ; Seidl, C.* ; Blechert, B.* ; Gaertner, F.C.* ; Gilbertz, K.P.* ; Fernandez, V.* ; Bassermann, F.* ; Endell, J.* ; Boxhammer, R.* ; Leclair, S.* ; Vallon, M.* ; Aichler, M. ; Feuchtinger, A. ; Bruchertseifer, F.* ; Morgenstern, A.* ; Essler, M.*

α-Radioimmunotherapy with 213Bi-anti-CD38 immunoconjugates is effective in a mouse model of human multiple myeloma.

Oncotarget 6, 4692-4703 (2015)
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In spite of development of molecular therapeutics, multiple myeloma (MM) is fatal in most cases. CD38 is a promising target for selective treatment of MM. We tested radioimmunoconjugates consisting of the α-emitter 213Bi coupled to an anti-CD38 MAb in preclinical treatment of MM. Efficacy of 213Bi-anti-CD38-MAb was assayed towards different MM cell lines with regard to induction of DNA double-strand breaks, induction of apoptosis and initiation of cell cycle arrest. Moreover, mice bearing luciferase-expressing MM xenografts were treated with 213Bi-anti-CD38-MAb. Therapeutic efficacy was monitored by bioluminescence imaging, overall survival and histology. 213Bi-anti-CD38-MAb treatment induced DNA damage which did not result in activation of the G2 DNA-damage-response checkpoint, but instead in mitotic arrest and subsequent mitotic catastrophe. The anti-tumor effect of 213Bi-anti-CD38-MAb correlated with the expression level of CD38 in each MM cell line. In myeloma xenografts, treatment with 213Bi-anti-CD38-MAb suppressed tumor growth via induction of apoptosis in tumor tissue and significantly prolonged survival compared to controls. The major organ systems did not show any signs of 213Bi-induced toxicity. Preclinical treatment of MM with 213Bi-anti-CD38-MAb turned out as an effective therapeutic option.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Anti-cd38-mab ; Cell Death ; Multiple Myeloma Xenograft Model ; Opm2 Cells ; Radioimmunotherapy ; α-emitter 213bi; Randomized Controlled-trial; Stem-cell Transplantation; Monoclonal-antibody; Bone-marrow; Particle Immunotherapy; Therapy; Lymphoma; Leukemia; Radioimmunoconjugate; Inhibitors
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Zeitschrift OncoTarget
Quellenangaben Band: 6, Heft: 7, Seiten: 4692-4703 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Begutachtungsstatus Peer reviewed