In vivo and in vitro effects of a novel anti-Dkk1 neutralizing antibody in multiple myeloma

Samantha Pozzi, Mariateresa Fulciniti, Hua Yan, Sonia Vallet, Homare Eda, Kishan Patel, Loredana Santo, Diana Cirstea, Teru Hideshima, Linda Schirtzinge, Stuart Kuhstoss, Kenneth C. Anderson, Nikhil Munshi, David Scadden, Henry M. Kronenberg, Noopur Raje*

*Korrespondierende:r Autor:in für diese Arbeit

Publikation: Beitrag in Fachzeitschrift (peer-reviewed)Artikel in Fachzeitschrift

61 Zitate (Scopus)

Abstract

Over-expression of the protein Dickkopf-1 (Dkk1) has been associated with multiple myeloma bone disease. Previous reports with the use of anti-Dkk1 neutralizing Ab directed strategies have demonstrated a pro-anabolic effect with associated anti-myeloma activity in 2 in vivo mouse models. However new insights on the role of the wnt pathway in osteoclasts (OC) are emerging and the potential effect of a neutralizing Ab to Dkk1 in osteoclastogenesis remains to be elucidated. In order to better define the effect of an anti-Dkk1 neutralizing Ab on osteoclastogenesis and myeloma, we studied a novel anti-Dkk1 monoclonal Ab in our preclinical models. In vivo data confirmed the pro-anabolic and anti-MM effect. In vitro data in part confirmed the in vivo observation, suggesting an indirect anti-MM effect secondary to inhibition of osteoclastogenesis and thus the interaction between MM and bone microenvironment. However, when studies on osteoclastogenesis were extended to samples derived from MM patients, we observed a variable response to anti-Dkk1 treatment without correlation to expression of surface receptors for Dkk1 in OCs suggesting potential heterogeneity in the efficacy of such a strategy. In conclusion, Dkk1 is a promising target for the treatment of both MM and bone disease, and ongoing clinical studies will help elucidate its efficacy.

OriginalspracheEnglisch
Seiten (von - bis)487-496
Seitenumfang10
FachzeitschriftBone
Jahrgang53
Ausgabenummer2
DOIs
PublikationsstatusVeröffentlicht - Apr. 2013
Extern publiziertJa

ASJC Scopus Sachgebiete

  • Endokrinologie, Diabetes und Stoffwechsel
  • Physiologie
  • Histologie

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