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.

Potential Commercial Applications:		Competitive Advantages:
Therapeutic for the treatment of various human diseases associated with aberrant cell growth and motility such as breast, prostate, and leukemia carcinomas. Research regent to study IGF-I and/or IGF-II binding and its association with tumor growth.		Antibodies against the ligands IGF-I and IGF-II, such as this invention, inhibit the interaction with IGF-IR yet likely do not have the type of toxicity associated with IGF-1R antibodies. High concentrations of IGF-II are found in cancer patients, on average several fold higher than IGF-I, thus this cross-reacting IGF-I/IGF-II antibody could be more effective than existing IGF-IR and/or IGF-I currently in the clinic. This novel IGF antibody may provide therapeutic intervention for multiple carcinomas.

Development Stage:
Discovery (Lead Identification)

Related Invention(s):
E-217-2005
E-336-2005


Inventors:

Dimiter Dimitrov (NCI)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 9676846 issued 2017-06-13

Publications:
Zhao Q, et al.; Human monoclonal antibody fragments binding to insulin-like growth factors 1 and 2 with picomolar affinity. PMID 21750218
Feng Y, et al.; Novel human monoclonal antibodies to insulin-like growth factor (IGF)-II that potently inhibit the IGF receptor type I signal transduction function. PMID 18283605
Kimura T, et al.; Targeting of bone-derived insulin-like growth factor-II by a human neutralizing antibody suppresses the growth of prostate cancer cells in a human bone environment. PMID 20028742

Collaboration Opportunity:
Licensing only


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-068-2011
Updated: May 4, 2018