Ich habe was zum Novartis-Morphosys-AK-Projekt BHQ880 zusammengetragen:
Bilanzpressekonferenz 28.2.2008 Seite 13: BHQ880 wird als MOR-Projekt bei Novartis offengelegt
BHQ880 tuact jetzt auch immer in den Novartis Clinical trial Listen auf:
Novartis Oncology – Leadership in Cancer and Hematology That Changes Patients’ Lives Highlights of Key Data Presented at ASH 2007 December 12, 2007 Seite 11(21) BHQ880 gegen solide Tumore in P1 befindlich
BHQ880 ist ein anti-DKK1 MAb wie aus folgendem aktuellen abstract hervorgeht:
2008 AACR Annual Meeting
April 12-16, 2008 San Diego, CA
bei Suche Morphosys
Abstract Number: 3987 Session Title: Antibodies Presentation Title: BHQ880, a novel anti-DKK1 neutralizing antibody, inhibits tumor-induced osteolytic bone disease Presentation Start/End Time: Tuesday, Apr 15, 2008, 8:00 AM -12:00 PM Location: Exhibit Hall B-F, San Diego Convention Center Poster Section: 28 Poster Board Number: 15 Author Block: Seth A. Ettenberg, Feng Cong, Janine Shulok, Stefanie Urlinger, Michael Bardroff, Olga Charlat, Yuji Mishina, Shanming Liu, Michael Daley, Sharon Li, Renee Walsh, Georges Rawadi, Philippe Clément-Lacroix, Patrick Mollat, Youzhen Wang, Yung-Mae Yao, David Stover. Novartis Institutes for Biomedical Research, Cambridge, MA, MorphoSys AG, Martinsried/Planegg, Germany, Galapagos, Romanville, France
Several cancers have a pathology which includes lytic bone disease. In particular, Multiple Myeloma (MM) patients often develop debilitating bone pain and fractures from osteolytic lesions. Recent publications have demonstrated elevated levels of DKK1 in the serum of MM patients, and this is correlated with an increase in osteolytic lesions. DKK1 is also elevated in patients with other tumor types that give rise to osteolytic metastases, such as breast and prostate cancers. DKK1 is a negative regulator of the canonical Wnt signaling pathway, which is a critical mediator of osteoblast differentiation and survival. We have identified a fully human IgG1λ monoclonal antibody (BHQ880) that potently and selectively neutralizes DKK1 suppression of Wnt signaling. BHQ880 was selected based on its high affinity for human, mouse, rat, and monkey DKK1 using MorphoSys´ HuCAL GOLD® phage display library. BHQ880 neutralizes DKK1 suppression of Wnt signaling in a TCF luciferase reporter assay. Furthermore, BHQ880 reactivates the production of Alkaline Phosphatase from DKK1-suppressed, osteoblast-like, mouse embryonic fibroblast cells (C3H10T1/2). BHQ880 binds within the Cys-2 domain of DKK1 and inhibits the interaction between DKK1 and both LRP5 and LRP6. BHQ880 has demonstrated potent efficacy in several models of tumor-induced osteolytic disease. These include two models of osteolytic metastasis that express high levels of DKK1, an intratibial prostate (PC3M-2AC6) tumor model in mice and an osteolytic breast tumor (MDA-MB-231) model using both intratibial and systemic delivery. Additionally, BHQ880 significantly inhibited bone loss in a systemic MM model (MMIS). In all three models, BHQ880 protected mice from tumor induced bone loss. These data highlight the potential for anti-DKK1 therapy in tumor induced osteolytic bone disease.
AACR = American Association for Cancer Research |