Case ID:
1999-0210
Web Published:
10/6/2011
Pharmaceutical Targeting of
Eosinophils by CCR-3 Medicated Internalization
(CHMC Ref. Id: 1999-0210)
Overview:
Eosinophils normally appear in peripheral blood at a concentration of ~1-3%
of total leukocytes and their presence in tissue is primarily restricted to the
mucosa. However, in various disease states, such as eosinophilic esophagitis
(EoE), eosinophils appear in increased numbers in peripheral blood and/or
tissues, a condition known as eosinophilia. Tissue accumulation of eosinophils
may cause potent pro-inflammatory effects. Numerous pharmacologic agents such as
glucocorticoids, have been used to treat a variety of eosinophil-related
diseases; however, none are specifically targeted to eosinophils.
Researchers at Cincinnati Children's have discovered methods that
specifically target eosinophil function and trafficking by using intracellular
targeting via the CC chemokine receptor-3 (CCR3), a major chemokine receptor on
eosinophils. The method involves providing a ligand for CCR3 that forms a
ligand-receptor complex, which is internalized into the cell, and then can alter
the cells function. The ligand may also have a compound attached to it, such as
a toxin, drug, enzyme, radiomolecule, which may be activated intracellularly.
Such methods can be designed to alter a specific cellular function or kill the
cell as appropriate.
Applications:
- Therapeutic for eosinophilic-related diseases and other allergic and
inflammatory disorders
- Methods may also be applicable to diseases or conditions involving
basophils, lymphocytes, and/or microglial cells
Advantages:
- Direct therapeutic for eosinophil-related diseases and other inflammatory
disorders
- Therapeutic specifically targeted to eosinophils (or basophils,
lymphocytes, and/or microglial cells)
- Increased therapy effectiveness
Patent Information:
- Patent Issued (US 6,358,697)
Cincinnati Children's Lead
Inventor:
Marc Rothenberg, M.D., PhD
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