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Dive into the research topics where Elisabeth Thomassen-Wolf is active.

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Featured researches published by Elisabeth Thomassen-Wolf.


Nature Medicine | 2002

Fully human, HLA-DR-specific monoclonal antibodies efficiently induce programmed death of malignant lymphoid cells

Zoltan Nagy; Bernd Hubner; Corinna Löhning; Robert Rauchenberger; Silke Reiffert; Elisabeth Thomassen-Wolf; Stefan Zahn; Sigmar Leyer; Eva M. Schier; Angelika Zahradnik; Christoph Brunner; Kurt Lobenwein; Benno Rattel; Michael Stanglmaier; Michael Hallek; Mark Wing; Steve Anderson; Matt Dunn; Titus Kretzschmar; Michael Tesar

The Human Combinatorial Antibody Library (HuCAL) was screened for antibodies specific to human leukocyte antigen-DR (HLA-DR) that induce programmed death of lymphoma/leukemia cells expressing the target antigen. The active Fab fragments were affinity-matured, and engineered to IgG4 antibodies of sub-nanomolar affinity. The antibodies exhibited potent in vitro tumoricidal activity on several lymphoma and leukemia cell lines and on chronic lymphocytic leukemia patient samples. They were also active in vivo in xenograft models of non-Hodgkin lymphoma. Cell death occurred rapidly, without the need for exogenous immunological effector mechanisms, and was selective to activated/tumor-transformed cells. Although the expression of HLA-DR on normal hematopoietic cells is a potential safety concern, the antibodies caused no long-lasting hematological toxicity in primates, in vivo. Such monoclonal antibodies offer the potential for a novel therapeutic approach to lymphoid malignancies.


Journal of Biological Chemistry | 2003

Human Combinatorial Fab Library Yielding Specific and Functional Antibodies against the Human Fibroblast Growth Factor Receptor 3

Robert Rauchenberger; Eric Borges; Elisabeth Thomassen-Wolf; Eran Rom; Rivka Adar; Yael Yaniv; Michael Malka; Irina Chumakov; Sarit Kotzer; Dalia Resnitzky; Achim Knappik; Silke Reiffert; Josef Prassler; Karin Jury; Dirk Waldherr; Susanne Bauer; Titus Kretzschmar; Avner Yayon; Christine Rothe

The human combinatorial antibody library Fab 1 (HuCAL®-Fab 1) was generated by transferring the heavy and light chain variable regions from the previously constructed single-chain Fv library (Knappik, A., Ge, L., Honegger, A., Pack, P., Fischer, M., Wellnhofer, G., Hoess, A., Wölle, J., Plückthun, A., and Virnekäs, B. (2000) J. Mol. Biol. 296, 57–86), diversified in both complementarity-determining regions 3 into a novel Fab display vector, yielding 2.1 × 1010 different antibody fragments. The modularity has been retained in the Fab display and screening plasmids, ensuring rapid conversion into various antibody formats as well as antibody optimization using prebuilt maturation cassettes. HuCAL®-Fab 1 was challenged against the human fibroblast growth factor receptor 3, a potential therapeutic antibody target, against which, to the best of our knowledge, no functional antibodies could be generated so far. A unique screening mode was designed utilizing recombinant functional proteins and cell lines differentially expressing fibroblast growth factor receptor isoforms diversified in expression and receptor dependence. Specific Fab fragments with subnanomolar affinities were isolated by selection without any maturation steps as determined by fluorescence flow cytometry. Some of the selected Fab fragments completely inhibit target-mediated cell proliferation, rendering them the first monoclonal antibodies against fibroblast growth factor receptors having significant function blocking activity. This study validates HuCAL®-Fab 1 as a valuable source for the generation of target-specific antibodies for therapeutic applications.


Molecular Immunology | 2008

In vitro affinity maturation of human GM-CSF antibodies by targeted CDR-diversification.

Stefan Steidl; Olaf Ratsch; Bodo Brocks; Manuela Dürr; Elisabeth Thomassen-Wolf

The mammalian immune system applies somatic hypermutation to select for antibodies with improved dissociation rates in vivo up to an intrinsic limit, previously termed as affinity ceiling. However, for certain therapeutic applications it may be desirable to further improve antibody affinities beyond that limit. In this study the selection of antibodies specific for the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) from the HuCAL GOLD human antibody library is described. In order to increase affinity and also functional activity, in vitro affinity maturation of a pool of lead Fab candidates was carried out. CDR-L3 and parallel CDR-H2 diversification using trinucleotide consensus cassettes were followed by the combination of optimized CDR-L3 and CDR-H2 leading to a 5000-fold improved affinity finally reaching a K(D) of 400 fM. Cytokine neutralizing potential of MOR04357 was evaluated in a TF-1 proliferation assay. Along with affinity optimization a 2000-fold increase in potency was observed compared to the parental antibody. Due to species cross-reactivity MOR04357 also blocks rat GM-CSF induced proliferation of FDCP-1 cells. Receptor inhibition studies showed that MOR04357 prevents the interaction of GM-CSF with the GM-CSF receptor alpha chain. As a consequence this leads to a blockade in signal transduction as measured by abolished STAT5 phosphorylation in the presence of GM-CSF and antibody. Due to its pro-inflammatory role GM-CSF has been implicated in the pathophysiology of inflammatory diseases like rheumatoid arthritis or asthma. Based on the mode of action described herein MOR04357 shows favourable antibody features as a potential drug candidate.


Archive | 2002

Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof

Avner Yayon; Eran Rom; Elisabeth Thomassen-Wolf; Eric Borges


Archive | 2006

Anti-GM-CSF Antibodies and uses therefor

Stefan Steidl; Elisabeth Thomassen-Wolf


Archive | 2001

Human polypeptides causing or leading to the killing of cells including lymphoid tumor cells

Zoltan Nagy; Christoph Brunner; Michael Tesar; Elisabeth Thomassen-Wolf


Archive | 2001

Immunomodulatory human mhc class ii antigen-binding polypeptides

Zoltan Nagy; Michael Tesar; Elisabeth Thomassen-Wolf


Archive | 2010

Treatment for multiple sclerosis

Stefan Steidl; Manuela Dürr; Elisabeth Thomassen-Wolf; Matthew Downham; Robert Friesen


Archive | 2000

Immunomodulatory human MHC class II antigen-binding peptides/proteins

Michael Tesar; Elisabeth Thomassen-Wolf; Nagy Zoltan


Archive | 2002

Antibodies that block fgfr3 activation, methods of screening for and uses thereof

Eric Borges; Eran Rom; Elisabeth Thomassen-Wolf; Avner Yayon

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Eric Borges

University of Münster

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Avner Yayon

Weizmann Institute of Science

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Eran Rom

Weizmann Institute of Science

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