Identification and characterization of three (3) novel fully human monoclonal antibodies, which may be used to prevent binding of IGF-I to its concomitant receptor IGFIR, consequently, modulating diseases such as cancer.

Cancer is one of the leading causes of death in United States and it is estimated that there will be approximately 600,000 deaths caused by cancer in 2006. A major drawback of the current chemotherapy-based therapeutics is the cytotoxic side-effects associated with them. Thus there is a dire need to develop new therapeutic strategies with fewer side-effects. Monoclonal antibody-based therapies have taken a lead among the new cancer therapeutic approaches.

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 three (3) novel fully human monoclonal antibodies designated m705, m706, and m708, which are specific for insulin-like growth factor (IGF)-I. Two (2) of the three (3) 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 to its concomitant receptor IGFIR, consequently, modulating diseases such as cancer. Additional embodiments describe methods for treating various human diseases associated with aberrant cell growth and motility including breast, prostate, and leukemia carcinomas. Thus, these novel IGF-I antibodies may provide a therapeutic intervention for multiple carcinomas.

Development Status:
The technology is in the pre-clinical stage; animal studies are currently under way.

Publications:

1. A manuscript from the IGF-I work is in preparation (Copy can be provided with Confidential Disclosure Agreement)
2. Y Feng, Z Zhu, X Xiao, V Choudhry, JC Barrett, DS Dimitrov. Novel human monoclonal antibodies to insulin-like growth factor (IGF)-II that potently inhibit the IGF receptor type I signal transduction function. Mol Cancer Ther. 2006 Jan;5(1):114-120.  [PubMed abs]

Preclinical

U.S. Provisional Application No. 60/790,512 filed 07 Apr 2006 (HHS Reference No. E-336-2005/0-US-01)

PCT Application No. PCT/US2007/066180 filed 07 Apr 2007, which published as WO 2007/118214 on 18 Oct 2007 (HHS Reference No. E-336-2005/0-PCT-02)

U.S. Patent Application No. 12/296,328 filed 07 Oct 2008 (HHS Reference No. E-336-2005/0-US-07)

International rights available.

Inventors:
Dimiter S. Dimitrov and Zhongyu Zhu (NCI)

Licensees Sought:
Available for licensing.

Collaborative Research Opportunity:
The NCI Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize monoclonal antibodies to treat human diseases. Please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov or by phone at 301-435-3121 for more information.