Therapeutics Based On The Induced Internalization Of Surface Receptors
Background:
The National Cancer Institute, Laboratory of Cellular Oncology is
seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate,
or commercialize therapeutics for diseases or conditions associated
with target receptors, such as cancer, angiogenesis, or HIV
infections.
Technology:
Cell-surface receptors are responsible for the biological
activities of many molecules. Specific ligands bind to them,
causing the cell-surface receptors to internalize or bring the
receptor and ligand inside the cell. A number of diseases,
including cancer, metabolic disorders, and viral infections are
known to require the expression of cell-surface receptors for
critical pathogenetic steps. This has prompted significant research
efforts toward the development of pharmaceutical agents that block
the signals from cell-surface receptors. While this current
research shows great promise, there is a strong need for new
therapeutic strategies that utilize the mechanistic properties of
cell-surface receptors.
This technology describes a strategy for artificially inducing the
internalization of surface receptors, and thereby blocking the
effects of the ligands associated with that receptor. This method
employs bifunctional ligands that bind to both a scavenger receptor
and a target receptor. As proof of concept, the inventors have
shown that a ligand capable of binding to the scavenger receptor
SREC-1 and the neuropilin-1 receptor NRP1 induces the
internalization of NRP1 and inhibits NRP1 signaling. This strategy
can be used to inhibit signaling from any target receptor if an
appropriate bifunctional ligand is used. This approach could be
used to limit tumor angiogenesis, limit tumor growth, block
metastasis formation, block inflammation, block viral infection,
and treat diseases where a cell surface receptor is identified as
the molecular basis for disease.
Further R&D Needed: Development
of therapeutic analogues and test for efficacy and toxicity.
R&D Status: Pre-clinical
development.
IP Status: U.S. Provisional
Application No. 61/023,397 filed 24 Jan 2008
Value Proposition:
- Method of inducing the internalization of target receptors
- Ability to inhibit numerous diseases associated with target
receptors such as HIV infection and cancer
Contact Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Tel: 301-435-3121
Email: hewesj@mail.nih.gov
Please reference advertisement # 763
Revised 12/29/2008