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

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.

TEILUF K;  SEIDL C.;  BLECHERT B.;  GAERTNER F. C.;  GILBERTZ K.P.;  FERNANDEZ V;  BASSERMANN F;  ENDELL J;  BOXHAMMER R;  LECLAIR Stephane;  VALLON M.;  AICHLER M;  FEUCHTINGER A;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  ESSLER M.; 

2015-07-13

IMPACT JOURNALS LLC

JRC93331

1949-2553,   

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,    https://publications.jrc.ec.europa.eu/repository/handle/JRC93331,