Monospecific and Bispecific Human Monoclonal Antibodies Targeting IGF-II
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 two monoclonal antibodies, designated m610.27 and m630, and a bispecific monoclonal antibody, m660, generated by linking domains from m610.27 and m630. All three antibodies display high affinities for IGF-I and IGF-II in the pM to nM range. The antibodies 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. m610.27 and m630 are the first pair of human antibodies that target nonoverlapping epitopes on IGF-II. All three antibodies in an IgG1 or IgG1-like format could lead to irreversible elimination of IGF-II from circulation making it a viable candidate for cancer treatment.
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Dimiter Dimitrov (NCI)
Yang Feng (NCI)
Weizao Chen (NCI)
US Application No. 61/548,164
PCT Application No. PCT/US2012060443
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Whitney Hastings ,
NIH Office of Technology Transfer
OTT Reference No: E-212-2011/0