Co-development Opportunity in Cancer Therapeutics: IGF1/IGF-2-Targeting Antibodies
Reference No: E-217-2005
Therapeutic, cancer, insulin-like
growth factor, IGF, antibody, mAb, dAb
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
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.
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)
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.
Preclinical (in vitro
and in vivo
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: firstname.lastname@example.org.
Whitney Hastings, NIH Office of Technology Transfer, Tel: (301)
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