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Novel Human IGF-I-Specific And IGF-I, IGF-II Cross-Reactive Antibodies As Potential Anti-Tumor Agents

Background:
The National Cancer Institute's Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize IGF-I-specific monoclonal antibodies.

A major drawback of current chemotherapy-based therapeutics is the cytotoxic side-effects associated with them. Monoclonal antibody-based therapies have taken a lead among the new cancer therapeutic approaches with fewer side-effects.

Technology:
The type 1 insulin-like growth factor 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 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 describes the identification and characterization of three novel fully human monoclonal antibodies designated m705, m706, and m708, which are specific for insulin-like growth factor (IGF)-I. Two of the three antibodies (m705 and m706) are specific for IGF-I and do not cross react with IGF-II and insulin while, m708 cross reacts with IGF-II. These antibodies can be used to prevent binding of IGF-I and IGF-II to the IGFIR receptor, consequently modulating diseases such as cancer. The invention also describes methods for treating various human diseases associated with aberrant cell growth and motility including breast, prostate, and leukemia carcinomas.  

Potential Commercial Applications/Possible Markets Identified:

• Therapeutics for multiple types of carcinomas

• Fully human antibodies reduce the probability for immune responses and cytotoxic side effects    
• Provides cross reacting and non-cross reacting antibodies for a broader range of therapeutic strategies

• Test antibodies in animal models of cancer and in human clinical trials
• Test antibodies in combination with other antibodies that have been already approved for treatment, including herceptin