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Therapeutic strategies for harnessing human eosinophils in allergic inflammation, hypereosinophilic disorders, and cancer.

ABSTRACT: The eosinophil is a multifunctional granulocyte best known for providing host defense against parasites. Paradoxically, eosinophils are also implicated in the pathogenesis of allergic inflammation, asthma, and hypereosinophilic syndromes. Emerging evidence also supports the potential for harnessing the cytotoxic power of eosinophils and redirecting it to kill solid tumors. Central to eosinophil physiology is interleukin-5 (IL-5) and its receptor (IL-5R) which is composed of a ligand-specific alpha chain (IL-5R?) and the common beta chain (?c). Eosinophil activation can lead to their degranulation, resulting in rapid release of an arsenal of tissue-destructive proinflammatory mediators and cytotoxic proteins that can be both beneficial and detrimental to the host. This review discusses eosinophil immunobiology and therapeutic strategies for targeting of IL-5 and IL-5R, as well as the potential for harnessing eosinophil cytotoxicity as a tumoricide.

SUBMITTER: Amini-Vaughan ZJ

PROVIDER: S-EPMC3729434 | biostudies-other | 2012 Oct

REPOSITORIES: biostudies-other

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Therapeutic strategies for harnessing human eosinophils in allergic inflammation, hypereosinophilic disorders, and cancer.

Amini-Vaughan Zhaleh J ZJ Martinez-Moczygemba Margarita M Huston David P DP

Current allergy and asthma reports 20121001 5

The eosinophil is a multifunctional granulocyte best known for providing host defense against parasites. Paradoxically, eosinophils are also implicated in the pathogenesis of allergic inflammation, asthma, and hypereosinophilic syndromes. Emerging evidence also supports the potential for harnessing the cytotoxic power of eosinophils and redirecting it to kill solid tumors. Central to eosinophil physiology is interleukin-5 (IL-5) and its receptor (IL-5R) which is composed of a ligand-specific alp ...[more]

PMID: 22875242

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Project description:Advances in understanding the immunological basis and mechanisms underlying allergic and immunologic disorders have led to effective but costly long-term and repetitive biologic therapies. Gene therapy is a rapidly advancing technology, in which a single administration of an adeno-associated virus encoding the therapeutic protein or monoclonal antibody may provide effective long-term therapy for allergic and immunologic disorders. In this review, we summarize the recent studies from our laboratory developing gene therapy strategies to treat hereditary angioedema and peanut allergy. The unraveling of the pathogenesis of immune-based disorders, including hereditary deficiencies of components of the immune system and allergic disorders, has led to the development of therapies using parenteral administration of recombinant proteins or monoclonal antibodies (1). While many of these therapies are highly effective, they are limited by the half-life of the therapeutic protein or antibody, requiring repetitive administration of days to weeks (2-15). The focus of recent work in our laboratory has been to solve this problem by substituting protein/monoclonal antibody administration with gene therapy, where current technology allows for a single administration of the gene coding for a protein or antibody to provide persistent expression of effective levels of the therapeutic protein or antibody. Gene therapy is a drug delivery platform which uses genetic material, usually in the form of coding exons of the therapeutic gene, to correct, compensate for, or prevent the development of an abnormal phenotype (16). Originally conceptualized as a strategy to treat rare hereditary disorders, gene therapy is being developed for a wide range of human disorders, including common acquired conditions (17-20). In this review, we will describe how we have adopted gene therapy technology to develop therapies for immune-related disorders, using as examples hereditary angioedema, an inherited autosomal dominant disorder, and peanut allergy, a common acquired allergic disorder.

Dataset Information

Therapeutic strategies for harnessing human eosinophils in allergic inflammation, hypereosinophilic disorders, and cancer.

Publications

Therapeutic strategies for harnessing human eosinophils in allergic inflammation, hypereosinophilic disorders, and cancer.

Similar Datasets

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