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

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

来源：Oncotarget, 2015, 6(7): 4692-4703.

• anti-CD38-MAb
• alpha-emitter Bi-213
• OPM2 cells
• radioimmunotherapy
• cell death
• multiple myeloma xenograft model

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 a-emitter Bi-213 coupled to an anti-CD38 MAb in preclinical treatment of MM. Efficacy of Bi-213-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 Bi-213-anti-CD38-MAb. Therapeutic efficacy was monitored by bioluminescence imaging, overall survival and histology. Bi-213-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 Bi-213-anti-CD38-MAb correlated with the expression level of CD38 in each MM cell line. In myeloma xenografts, treatment with Bi-213-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 Bi-213-induced toxicity. Preclinical treatment of MM with Bi-213-anti-CD38-MAb turned out as an effective therapeutic option.

• 出版日期2015-3-10