Title: α-Radioimmunotherapy with 213Bi-anti-CD38 immunoconjugates is effective in a mouse model of human multiple myeloma
Authors: TEILUF KSEIDL C.BLECHERT B.GAERTNER F. C.GILBERTZ K.-P.FERNANDEZ VBASSERMANN FENDELL JBOXHAMMER RLECLAIR StephaneVALLON M.AICHLER MFEUCHTINGER ABRUCHERTSEIFER FrankMORGENSTERN AlfredESSLER M.
Citation: ONCOTARGET vol. 6 no. 7 p. 4692 - 4703
Publisher: IMPACT JOURNALS LLC
Publication Year: 2014
JRC N°: JRC93331
ISSN: 1949-2553
URI: www.impactjournals.com/oncotarget
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=2986&path%5B%5D=5691
http://publications.jrc.ec.europa.eu/repository/handle/JRC93331
Type: Articles in periodicals and books
Abstract: 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.
JRC Directorate:Nuclear Safety and Security

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