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 known receptor negatively modulates signal transduction through the IGF pathway and associated cell proliferation and growth. Therefore, use of humanized or fully human antibodies against IGFs represents a valid approach to inhibit tumor growth.
Researchers at the National Cancer Institute Cancer and Inflammation Program recently generated two monoclonal antibodies, designated m610.27 and m630, and a bispecific monoclonal antibody, m660, 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 non-overlapping 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.
- Therapeutic for the treatment of various human diseases associated with aberrant cell growth and motility such as breast, prostate, and leukemia cancers.
- Research reagent to study IGF-I and/or IGF-II binding and its association with tumor growth.
- m610.27 and m630 are the first characterized antibodies that target non-overlapping epitopes on IGF-II
- m660 was generated from two domains; one each from m610.27 and m630.
- Small size of the m610.27 and m630 domains prevent overlapping in binding to IGF-II.
Dimiter Dimitrov (NCI)
- U.S. Patent Issued: U.S. Patent Number 9,127,056, Issued 08 Sep 2015