Human Monoclonal Antibodies Cross-reacting to Insulin-like Growth Factors IGF-I and IGF-II as Potential Anti-tumor Agents

The National Cancer Institute's  Cancer and Inflammation Program is seeking statements of capability or interest from parties interested in licensing this technology. 

The type 1 insulin-like growth factor (IGF) receptor (IGF1R) is over-expressed by many tumors and mediates proliferation, motility, and protection from apoptosis. Agents that inhibit IGF1R expression or function can potentially block tumor growth and metastasis. Its major ligands, IGF-I, and IGF-II are over-expressed by multiple tumor types. Previous studies indicate that inhibition of IGF-I, and/or IGF-II binding to its cognizant receptor negatively modulates signal transduction through the IGF pathway and concomitant cell proliferation and growth. Therefore, use of humanized or fully human antibodies against IGFs represents a valid approach to inhibit tumor growth.

The present invention discloses the identification and characterization of a fully human monoclonal antibody designated m708.5 that has been affinity maturated against IGF-I and IGF-II and displays extremely high affinities for IGF-I and IGF-II in the picoM range.  The m708.5 antibody potently inhibited signal transduction mediated by the IGF-1R interaction with IGF-I and IGF-II and blocked phosphorylation of IGF-IR and the insulin receptor.  Further, this antibody inhibited migration in the MCF-7 breast cancer cell line at the picoM range.  Therefore, this antibody can be used to prevent binding of IGF-I and/or IGF-II to its concomitant receptor IGFIR, consequently, modulating diseases such as cancer.