Gene Therapy for Eosinophilic Disorders
- Detailed Technology Description
- This invention allows for the treatment of eosinophilic disorders by administration of an adeno-associated virus (AAV) expressing the genetic sequence for an anti-eosinophil monoclonal antibody.
- Others
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None
- *Abstract
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TechnologyOverview
Eosinophils are highly specialized, bone-marrow derived,granulocytic effector cells (white blood cells) that store and release severalhighly active mediators. They have been implicated in a variety of chronicallergic disorders, including asthma, eosinophilic esophagitis as well ascertain types of cancers and are characterized by persistent blood eosinophiliaand infiltration of eosinophils into the diseased organ, wherein they releasecellular mediators involved in disease pathogenesis.Eosinophilic disorders have largelybeen treated with chronic administration of corticosteroids; while ofteneffective, chronic corticosteroid therapy is commonly linked to numerousadverse effects. Monoclonal therapeutics have also been developed to: (1)reduce bone marrow eosinophil production by targeting eosinophil receptors; (2)induce eosinophil apoptosis; and (3) modulate eosinophil function.
While there has been some successwith anti-IL5 and anti-IL4/anti-ILI3 receptor monoclonals, this approachsuppresses only production, with no effect on tissue eosinophil accumulationsecondary to local signals in the diseased tissues. In contrast, while far lessattention has been paid to antibodies that induce eosinophil apoptosis, thereis compelling experimental animal data to demonstrate that anti-eosinophilantibodies not only reduce the numbers of blood eosinophils, but also thenumbers of bone marrow and tissue eosinophils.
The inventors have disclosed atechnology for the development of a therapeutic that induces apoptosis ofeosinophils. However, rather than using an anti-eosinophil monoclonal antibodywhich requires repeated parenteral administration to maintain anti-eosinophilefficacy, they disclose a novel gene therapy-based platform in which an AAVexpressing the genetic sequence for an anti-eosinophil monoclonal can be usedto genetically modify liver hepatocytes to express and secrete an anti-eosinophilmonoclonal which will function to induce apoptosis of bone marrow, blood andtissue eosinophils.
PotentialApplications
This in vivo gene therapy can be used to treat diseases with no knowncures, such as chronic eosinophilic leukemia-not otherwise specified (CEL-NOS).
Advantages
This technology is designed as aone-time therapy to suppress total body eosinophils in atopic individuals andwill provide sustained, long-term therapeutic benefit for the treatment ofeosinophilic disorders.
- *Licensing
- Brian J. Kelly, Directorbjk44@cornell.edu646-962-7045
- Country/Region
- USA
