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

Katharina Teiluf, Christof Seidl, Birgit Blechert, Florian C. Gaertner, Klaus Peter Gilbertz, Vanesa Fernandez, Florian Bassermann, Jan Endell, Rainer Boxhammer, Stephane Leclair, Mario Vallon, Michaela Aichler, Annette Feuchtinger, Frank Bruchertseifer, Alfred Morgenstern, Markus Essler

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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 luciferaseexpressing 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.

Original languageEnglish
Pages (from-to)4692-4703
Number of pages12
JournalOncotarget
Volume6
Issue number7
DOIs
StatePublished - 2015

Keywords

  • Anti-CD38-MAb
  • Cell death
  • Multiple myeloma xenograft model
  • OPM2 cells
  • Radioimmunotherapy
  • α-emitter Bi

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