Leading up to the Antibody Engineering Event, we'll be sharing the posters that will be featured in the Exhibit Hall. Antibody Engineering & Therapeutics will take place December 8-12, 2013 in Huntington Beach, California. For more information the program, download the agenda. If you'd like to join us, as a reader of this blog, when you register to join us and mention code XD13172BLOGJP, you'll save 20% off the standard rate!
Featured Poster: A Novel Bi-specific Antibody-Receptor Domain Fusion Protein That Simultaneously Targets IGF-IR and VEGF for Degradation in Tumor Cells
Featured Presenter: Yang Shen, ImClone Systems
About the poster: Monoclonal antibody (mAb) targeting of tumor-associated receptor tyrosine kinase (RTK)-mediated signaling pathways has been a proven therapeutic strategy for the treatment of cancer. Mounting evidence suggests that the combination of two or more mAbs inhibiting multiple RTK pathways offers a more effective approach than single agent. Bi-specific antibodies (BsAbs) or scaffold proteins which can simultaneously block two tumor targets has emerged as promising alternatives to antibody combinations. Here we describe the design and development of a novel fully human Bi-specific Antibody-receptor domain fusion molecule with ligand Capture (BiAbCap). The BiAbCap possesses potent neutralizing activities against Insulin-like Growth Factor – Type I Receptor (IGF-IR) and Vascular Endothelial Growth Factor (VEGF) in vitro and in vivo in model systems of human cancer. Through in vitro and cell based studies, we demonstrated that the BiAbCap is capable of cross-linking VEGF to IGF-IR and inducing co-internalization of both targets followed by degradation in tumor cells. In xenograft models, we have further demonstrated that the BiAbCap is capable of not only inhibiting tumor growth by direct inhibition of IGF-IR on tumors, but also acts as an anti-angiogenic agent by capturing circulating VEGF. In multiple xenograft tumor models in mice, the BiAbCap exhibited potent tumor inhibition, with efficacy superior to the combination of the two mono-specific (anti-IGF-IR and anti-VEGF) targeting agents. The “capture-for-degradation” mechanism demonstrated within this molecule is informative for the generation of more potent anti-cancer bi-functional therapies directed at multiple ligand-receptor mediated pathways, taking advantage of a novel co-internalization and degradation mechanism beyond ligand-receptor blockade.
|
Share this article with your social network, just click below to share now!
|
|
|
No comments :
Post a Comment