α-Radioimmunotherapy with 213Bi-anti-CD38 immunoconjugates is effective in a mouse model of human multiple myeloma
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Katharina Teiluf1,*, Christof Seidl1,2,*, Birgit Blechert1, Florian C. Gaertner1,3, Klaus-Peter Gilbertz4, Vanesa Fernandez5, Florian Bassermann5, Jan Endell6, Rainer Boxhammer6, Stephane Leclair6, Mario Vallon1,7, Michaela Aichler8, Annette Feuchtinger8, Frank Bruchertseifer9, Alfred Morgenstern9 and Markus Essler1,3
1 Department of Nuclear Medicine, Technische Universität München, Munich, Germany
2 Department of Obstetrics and Gynecology, Technische Universität München, Munich, Germany
3 Department of Nuclear Medicine, Universitätsklinikum Bonn, Bonn, Germany
4 Institute of Radiobiology, German Armed Forces, Munich, Germany
5 III. Medical Department, Technische Universität München, Munich, Germany
6 MorphoSys AG, Martinsried/Planegg, Germany
7 Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA
8 Institute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany
9 European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany
* These authors contributed equally to this work
Christof Seidl, email:
Keywords: anti-CD38-MAb, α-emitter 213Bi, OPM2 cells, radioimmunotherapy, cell death
Received: October 20, 2014 Accepted: December 09, 2014 Published: December 10, 2014
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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