Dual @entity7424 /II-neutralizing antibody MEDI-573 potently inhibits IGF signaling and XXXX growth.

@entity419 @entity5 @entity19 @entity7423 @entity3239 @entity10247 @entity7424
Insulin-like growth factors (IGF), @entity7424 and @entity10247 , are small polypeptides involved in regulating cell proliferation, survival, differentiation, and transformation. IGF activities are mediated through binding and activation of @entity7423 or @entity3239 ( @entity3239 ). The role of the @entity7423 pathway in promoting @entity5 growth and survival is well documented. Overexpression of @entity10247 and @entity3239 is reported in multiple types of @entity5 and is proposed as a potential mechanism for @entity5 cells to develop resistance to @entity7423 -targeting therapy. MEDI-573 is a fully human antibody that neutralizes both @entity7424 and @entity10247 and inhibits IGF signaling through both the @entity7423 and @entity3239 pathways. Here, we show that MEDI-573 blocks the binding of @entity7424 and @entity10247 to @entity7423 or @entity3239 , leading to the inhibition of IGF-induced signaling pathways and cell proliferation. MEDI-573 significantly inhibited the in vivo growth of @entity7424 - or @entity10247 -driven @entity5 . Pharmacodynamic analysis demonstrated inhibition of @entity7423 phosphorylation in @entity5 in @entity19 dosed with MEDI-573, indicating that the antitumor activity is mediated via inhibition of @entity7423 signaling pathways. Finally, MEDI-573 significantly decreased @entity419 ( @entity419 ) uptake in IGF-driven @entity5 models, highlighting the potential utility of @entity419 -PET as a noninvasive pharmacodynamic readout for evaluating the use of MEDI-573 in the clinic. Taken together, these results demonstrate that the inhibition of @entity7424 and @entity10247 ligands by MEDI-573 results in potent antitumor activity and offers an effective approach to selectively target both the @entity7423 and @entity3239 signaling pathways.
