DNA-based immunotherapeutics for the treatment of allergic disease

Authors

  • Anthony A. Horner,

    1. Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA.
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  • John H. Van Uden,

    1. Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA.
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  • Jose M. Zubeldia,

    1. Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA.
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  • David Broide,

    1. Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA.
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  • Eyal Raz

    1. Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA.
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Correspondence to: Eyal Raz
Department of Medicine
University of California, San Diego
9500 Gilman Drive
La Jolla
CA 92093-0663
USA
Fax: 858 534 5399
e-mail: eraz@ucsd.edu

Abstract

Summary: Allergic diseases are a growing health concern in industrialized countries. Despite a number of effective therapeutic options for the prevention and treatment of the pathophysiologic responses which characterize allergic diseases, the induction of true allergen desensitization remains an elusive therapeutic goal. Only immunotherapy (IT) has been shown to have any effect on the underlying hypersensitivities which mediate allergic reactions, and traditional protein-based allergen IT has a limited scope of efficacy. However, a number of reagents collectively termed DNA-based immunotherapeutics have proven highly effective in both the prevention and reversal of Th2-mediated hypersensitivity states in mouse models of allergic disease. Four basic DNA-based immunotherapeutic modalities have been used for these studies. These include immunization with gene vaccines, allergen mixed with immunostimulatory oligodeoxynucleotide (ISS-ODN), and physical allergen–ISS-ODN conjugates (AIC), as well as immunomodulation with ISS-ODN alone. Results from many laboratories have generated guarded optimism that DNA-based immunotherapeutics may be effective for the reversal of allergic hypersensitivity states in humans, and several clinical trials have already been initiated. This review will focus on our present understanding of the biological activities of DNA-based immunotherapeutics and their application to the treatment of allergic diseases.

This work was supported by grants AI40682 and AI01490 from the NIH and by a grant from Dynavax Technologies Corporation. J.H.V. is also a Medical Scientist Training Program Trainee.

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