Overview

Our projects are located in the field of molecular allergology and immunology and mainly focus on the translation of basic research into clinical application.

  • Molecular Biology and Biochemistry
  • Recombinant Technologies
  • Immunomodulation
  • Allergy and Allergens
  • Cross-reactive Carbohydrate Determinants (CCDs)
  • Molecule Design
  • Antibody Engineering

 

 

Concept for tolerance induction. Source: Blank.

Immunomodulation

Although specific immunotherapy in many cases represents an effective treatment, therapy failures happen and patient compliance is low due to long treatment times. Our goal is the development of novel immune modulators and local application forms to find an effective and long lasting cure for immune diseases. For shifting immune balance from a state of disease to a tolerogenic state we combine the allergen-specific immunotherapy with the local support of the induction of regulatory T cells at the site of allergen presentation by using immunomodulatory adjuvant molecules. Moreover, for this purpose we are developing strategies for the local application of the active substances to create a tolerogenic microenvironment at the site of allergen presentation.

 

Recombinant Allergens

The aim of different projects is the identification, characterization and engineering of allergens, especially in the field of venom allergy. In addition to the molecular interaction of allergens with specific antibodies and associated receptors we mainly focus on diagnostic and therapeutic questions.

Anaphylaxis due to Hymenoptera stings is one of the most severe clinical outcomes of IgE-mediated hypersensitivity reactions. Although allergic reactions to Hymenoptera stings are often considered as a general model for the underlying principles of allergic disease, diagnostic tests are still hampered by a lack of specificity and venom immunotherapy by severe systemic side-effects and incomplete protection.

Thus, aim of our work is the improvement of both diagnostic and therapeutic approaches by recombinant technologies. Since a recombinant availability of venom allergens might offer several promising possibilities for an improvement, our work focuses on the identification of novel allergenic components from different insect venoms as well as on the recombinant expression and detailed characterization of established allergens. Our work demonstrates that the availability of the newly identified and established recombinant allergens has the potential to contribute to an improved component-resolved diagnosis and therapeutic monitoring in venom allergy and to the understanding of the allergological mechanisms.

 

Cross-reactive Carbohydrate Determinants (CCDs)

CCDs represent the carbohydrate structures that are most frequently recognized by humoral immune responses. They do not only interfere with diagnosis of allergic and parasitic diseases but also can lead to clinical effects up to life-threatening anaphylactic reactions. The analysis of underlying mechanisms and reasons for sometimes missing clinical effects is the goal of other projects. Our work for example addresses allergenic cross-reactivity using a recombinant approach by employing cell lines with variant capacities of alpha-1,3-core fucosylation, the causative structure for CCD reactivity in venom allergy. To date, in vitro diagnosis of hymenoptera venom allergy using venom extracts is employed routinely, but remains severely affected by molecular cross-reactivity and false-positive test results. About 30-50% of patients with insect venom allergy have IgE antibodies that react with both honeybee and wasp venom. Apart from true double sensitization, IgE against cross-reactive carbohydrate determinants (CCD) are the most frequent cause of multiple reactivities severely hampering the diagnosis of hymenoptera venom allergy and the design of therapeutic strategies by clinically irrelevant test results. Using our approach, a novel diagnostic concept was introduced by the production of properly glycosylated allergens allowing reliable differentiation of protein versus cross-reactive carbohydrate determinant (CCD) reactivity and enabling identification of true sensitization with clinical impact.

 

Antibody engineering

Allergen-specific IgE and IgG antibodies play pivotal roles in the induction and progression of allergic hypersensitivity reactions. Consequently, monoclonal human IgE and IgG4 antibodies with defined specificity for allergens will be useful in allergy research and diagnostic tests. Hence, we recombinantly produce allergen-specific monoclonal antibodies and antibody derivatives of various isotypes that can be used in diagnostic settings and are attractive tools for basic and applied research to evaluate the complex molecular interplay of allergens, specific antibodies and Fc receptors and to better understand the modulation of the allergic reaction.

Contact

PD Dr. rer. nat. Simon Blank

Zentrum Allergie und Umwelt (ZAUM)
Technische Universität und Helmholtz Zentrum München


Ingolstädter Landstr. 1
85764 Neuherberg

Phone: +49 89 3187-2625
E-mail: Simon.blanknoSp@m@helmholtz-muenchen.de