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Human Monoclonal Antibodies Cross-reacting to Insulin-like Growth Factors IGF-I and IGF-II as Potential Anti-tumor Agents

Posted Aug 29 2011 8:00pm

Description of Invention:
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.

Applications:
  • 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.


Advantages:
  • 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 Status:
  • Pre-clinical
  • In vitro data available


Inventors:
Dimiter S Dimitrov (NCI)
Zhongyu Zhu (NCI)
Qi Zhao (NCI)


Patent Status:
HHS, Reference No. E-068-2011/0
US, Application No. 61/474,664 filed 12 Apr 2011


Related Technologies:
US, Application No. 12/296,328 filed 07 Oct 2008, Reference No. E-336-2005/0 ; Antibody Compositions and Methods for Treatment of Neoplastic Disease
US, Patent No. 7,824,681, Issued 02 Nov 2010, Reference No. E-217-2005/2 ; Human Monoclonal Antibodies that Specifically Bind IGF-II
PCT, Application No. PCT/US2007/066180 filed 06 Apr 2007, Reference No. E-336-2005/0


Relevant Publication:
  1. Zhao Q, et al. [ PMID 21750218 ]
  2. Feng Y, et al. [ PMID 18283605 ]
  3. Kimura T, et al. [ PMID 20028742 ]


Collaborative Research Opportunity:
The NCI CCR Nanobiology Program, Protein Interaction Group, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov .


For Licensing Information Please Contact:
Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: hastingw@mail.nih.gov
Phone: 301-451-7337
Fax: 301-402-0220


Ref No: 2309

Updated: 08/2011

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