Antigen-specific targeting and elimination of EBV-transformed B cells by allergen toxins.

Abstract

BACKGROUND:

With the exception of antigen-specific immunotherapy, current treatments for atopic diseases provide only symptomatic relief. Because of the increasing incidence of such diseases, the development of novel strategies and concepts for the treatment of allergies is urgently needed.

OBJECTIVE:

Here we present a new approach for the treatment of atopic diseases. The strategy is comparable to the application of immunotoxins in cancer therapy, in which a cytotoxic peptide is coupled to a cancer cell-specific antibody fragment or ligand. In the case of so-called allergen toxins (ATs), the target cell-specific moiety is an allergen or allergen-derived fragment, which should be bound only by allergen-reactive cells. After receptor-mediated internalization, allergen-specific cells are killed, and the allergic pathogenesis is interrupted.

METHODS:

Proof of the AT principle was shown by using a human ex vivo system in which EBV was used to transform human B cells specific for the timothy grass pollen allergen Phl p 5b. The AT is composed of the major B-cell and T-cell epitopes of the Phl p 5b (P5) allergen fused to a truncated form of the highly toxic Pseudomonas aeruginosa exotoxin A (ETA').

RESULTS:

Allergen-specific and nonspecific B cells were challenged with P5-ETA', but only the Phl p 5b-reactive B cells showed selective binding and cytotoxicity.

CONCLUSION:

This approach represents an initial step toward a novel therapeutic strategy in the treatment of atopic diseases.

• Authors: Michael Stöcker, Torsten Klockenbring, Michael Huhn, Thomas Nachreiner, Daniel Wicklein, Arnd Petersen, Ralf Bauer, Roland Goerlich, Rainer Fischer, Stefan Barth
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 116 Issue 4 Pg. 910-5 (Oct 2005) ISSN: 0091-6749 [Print] United States
• PMID: 16210069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Immunotoxins
• P5-ETA'
• Plant Proteins
• Recombinant Fusion Proteins
• Phl p Vb protein, Phleum pratense
• Ribonucleases

Topics

• Allergens (genetics, immunology)
• B-Lymphocytes (immunology, virology)
• Cell Transformation, Viral
• Cytotoxicity, Immunologic
• Herpesvirus 4, Human (immunology)
• Humans
• Hypersensitivity, Immediate (immunology, therapy)
• Immunotoxins (genetics, immunology, pharmacology)
• In Vitro Techniques
• Phleum (genetics, immunology)
• Plant Proteins (genetics, immunology)
• Recombinant Fusion Proteins (genetics, immunology, pharmacology)
• Ribonucleases (genetics, immunology)