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


CONCLUSIONS
This approach represents an initial step toward a novel therapeutic strategy in the treatment of atopic diseases.
Stöcker
Michael
M
University Aachen, Institute of Molecular Biotechnology, Aachen, Germany.
Klockenbring
Torsten
T
Huhn
Michael
M
Nachreiner
Thomas
T
Wicklein
Daniel
D
Petersen
Arnd
A
Bauer
Ralf
R
Goerlich
Roland
R
Fischer
Rainer
R
Barth
Stefan
S
D000485:Allergens / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000628:therapy; D000922:Immunotoxins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D066298:In Vitro Techniques; D031784:Phleum / Q000235:genetics / Q000276:immunology; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D012260:Ribonucleases / Q000235:genetics / Q000276:immunology
D000485:Allergens; D000922:Immunotoxins; C513565:P5-ETA'; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; C102306:Phl p Vb protein, Phleum pratense; D012260:Ribonucleases