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Co-development Opportunity in Cancer Therapeutics: IGF1/IGF-2-Targeting Antibodies

Keywords: Therapeutic, cancer, insulin-like growth factor,  IGF, antibody, mAb, dAb

Summary:
The National Cancer Institute's Nanobiology Program seeks parties interested in the co-development of IGF-1/IGF-2-targeting, fully human monoclonal antibodies, domain antibodies, and bi-specific antibodies to toward in vivo proof of concept. Outside parties may also exploit non-proprietary research tools to further modify and isolate these domain and monoclonal antibodies in collaboration with the NCI researchers.

Background:
The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system consists of two cell-surface receptors (IGF1R and IGF2R), two ligands (IGF-1 and IGF-2), a family of six high-affinity IGF-binding proteins (IGFBP 1-6), as well as associated IGFBP  proteases. Previous studies indicated that inhibition of IGF-1, and/or IGF-2 binding to their 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.

Technology:
Researchers at the National Cancer Institute have developed several domain antibodies and monoclonal antibodies specific to IGF-1 and/or IGF-2. In addition, they developed bi-specific antibodies that target non-overlapping epitopes of IGF-2 and several domain antibodies (dAbs) suitable for diagnostic purposes.

Domain antibodies (dAb). dAbs contain only one human-based variable domain with three complementarity determining regions (CDRs). Binding targets include IGF1R, IGF-2I, and both IGF-1 and IGF-2. Their 10-fold smaller size than IgG antibodies allows better penetration into the cell. The dAbs can be fused to polypeptides or drugs to provide fusion proteins or conjugates, and they can inhibit IGF1R function.

Monoclonal antibodies (mAb).  mAbs have been engineered to bind to IGF-1 and/or IGF-2, and some IGF-2 mAbs have nM range affinity. A bispecific mAb with nM range affinity is available that binds the non-overlapping targets of two anti-IGF-2 mAbs. For therapeutic applications, all mAbs prevent target(s) interaction with IGF1R.

R&D Status: Preclinical (in vitro and in vivo data available)

IP Status: US Patents 7,824,681; 8,071,323; US Patent Applications 61/249,476; 61/474,664; 61/548,164.

Information on co-development research: Please submit an information request form referencing E-217-2005 on http://techtransfer.cancer.gov, or contact: John D. Hewes, Ph.D., NCI Technology Transfer Center, Tel.: 301-435-3121, Email: hewesj@mail.nih.gov.
   
Licensing information: Please contact: Whitney Hastings, NIH Office of Technology Transfer, Tel: (301) 451-7337, Email:  hastingsw@mail.nih.gov.

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