Special Issue "Bispecific Antibodies for Dual Targeting Strategies"
QuicklinksA special issue of Antibodies (ISSN 2073-4468).
Deadline for manuscript submissions: closed (28 February 2013)
Special Issue Editor
Guest Editor
Prof. Dr. Roland Kontermann
Institut für Zellbiologie und Immunologie, Universität Stuttgart, Allmandring 31, D-70569 Stuttgart, Germany
Website: http://www.uni-stuttgart.de/izi/mitarbeiter/verzeichnis/roland.html
E-Mail: roland.kontermann@izi.uni-stuttgart.de
Interests: bifunctional antibody fusion proteins; half-life extension strategies; targeted nanoparticulate drug delivery systems
Special Issue Information
Dear Colleagues,
Bispecific antibodies are emerging as novel approach for dual targeting strategies combining two different antigen-binding sites within one molecules. Bispecific antibodies allow to improve binding, selectivity and efficacy, e.g. by simultaneously inhibiting two receptors or cytokines. A multitude of bispecific antibody formats have been developed in the recent years and novel applications have been established, including the dual retargeting of toxins, cytokines and growth factors with bispecific antibody fusion proteins but also dual retargeting of effector cells of the immune system with trispecific antibodies. Furthermore, dual targeting is applied to nanoparticles for delivery of drugs to target cells. Main indications include tumor therapy and the treatment of inflammatory diseases, but new areas for application of dual targeting strategies are also emerging, e.g. in diagnosis and imaging. Recent studies have already shown that bispecific antibodies show similar or even improved efficacy compared with combination therapy with two antibodies, thus offer an alternative to the parallel development, production and approval of two monoclonal antibodies.
This special issue of Antibodies addresses the growing interest in dual targeting strategies using bispecific antibodies and I kindly invite you to submit your novel results to this special issue. Welcome are manuscripts describing the application of bispecific antibodies for dual targeting strategies using in vitro and in vivo studies as well as manuscript dealing with novel bispecific antibody formats and fusion proteins suitable for dual targeting strategies.
Prof. Dr. Roland E. Kontermann
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed Open Access quarterly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
Keywords
- bispecific antibodies for dual targeting of tumor cells
- bispecific antibodies for dual neutralization of cytokines and growth factors
- bispecific antibodies for dual targeting for receptor activation
- bispecific antibodies for dual retargeting of cytokines and growth factors
- bispecific antibodies for dual retargeting of immune effector cells
- bispecific antibodies for dual retargeting of toxins
- antibodies for dual retargeting of nanoparticles and liposomes
- new bispecific antibody formats
- bispecific antibodies for tumor therapy
- bispecific antibodies for therapy of inflammatory diseases
- bispecific antibodies for therapy of infectious diseases
- bispecific antibodies for imaging and diagnosis
- bispecific antibodies for half-life extension
Published Papers (5 papers)
  Antibodies 2012, 1(1), 2-18; doi:10.3390/antib1010002
Received: 28 February 2012; in revised form: 16 March 2012 / Accepted: 30 March 2012 / Published: 10 April 2012
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Article:
A Cassette Vector System for the Rapid Cloning and Production of Bispecific Tetravalent Antibodies
Antibodies 2012, 1(1), 19-38; doi:10.3390/antib1010019
Received: 1 March 2012; in revised form: 28 March 2012 / Accepted: 30 March 2012 / Published: 11 April 2012
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Antibodies 2012, 1(2), 172-198; doi:10.3390/antib1020172
Received: 24 May 2012; in revised form: 27 June 2012 / Accepted: 10 July 2012 / Published: 18 July 2012
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Antibodies 2012, 1(2), 199-214; doi:10.3390/antib1020199
Received: 8 May 2012; in revised form: 9 July 2012 / Accepted: 13 July 2012 / Published: 25 July 2012
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Article:
Immunotherapy of B-Cell Lymphoma with an Engineered Bispecific Antibody Targeting CD19 and CD5
Antibodies 2013, 2(2), 338-352; doi:10.3390/antib2020338
Received: 26 March 2013; in revised form: 22 April 2013 / Accepted: 22 April 2013 / Published: 14 May 2013
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Planned Papers
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: Immunotherapy of B-Cell Lymphomas with a Recombinant Bispecific Antibody Targeting CD19 and CD5
Authors: Sandra Lüttgau, Dorothée Deppe, Saskia Meyer, Regina Fertig, Hossein Panjideh, Martin Lipp, Oliver Schmetzer, Antonio Pezzutto, Frank Breitling and Gerhard Moldenhauer
Affiliation: Department of Translational Immunology (D015), German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
Abstract: Monoclonal antibody therapy of non-Hodgkin’s lymphoma and a variety of solid tumors has proven to be rather successful. In particular bispecific antibodies (bsAb) are excellent activators of the immune system and have been generated against different combinations of tumor antigens and trigger molecules on effector cells. However, clinical use of bispecific antibodies is hampered for technical reasons, namely lengthy purification, expensive production engendered by the low yield, mouse origin of conventional antibodies, and their large molecular weight that hinders diffusion into solid tumors. Using genetic engineering a humanized Fab fragment with specificity for CD19 was fused to a disulfide-stabilized single-chain antibody (dsFv) recognizing CD5. This format should show reduced immunogenicity (because of human constant immunoglobulin domains) and improved tissue penetration (due to a MW of 80kDa versus 150 kDa for intact IgG). BsAb FabCD19xdsFvCD5 was produced in stably transfected HEK293T cells using MiniPerm modular bioreactors. Subsequent purification was performed by affinity chromatography over a rabbit anti-human IgG-Sepharose CL-4B column. Protein analysis revealed that bsAb was fully assembled and more than 90% pure. The specificity of bsAb FabCD19xdsFvCD5 binding to target cells was verified by flow cytometry using several cell lines expressing either CD19 or CD5. Binding affinities of both bsAb arms was compared with the bivalent parental antibodies against CD19 and CD5 by a FACS-based binding competition assay. BsAb-induced redirected lysis of B-lymphoma cells by activated PBMC from healthy donors was demonstrated in a chromium-release assay. A clear dose-response relationship could be established in the range of 0.1 and 1 mg/ml bsAb. To evaluate the in vivo efficacy of bsAb FabCD19xdsFvCD5, NOD/SCID mice were intravenously injected with luciferase transfected Raji lymphoma cells together with pre-activated PBMC. Mice received 5 injections of therapeutic or control antibodies and were monitored for 9 weeks by bioluminiscent imaging. While in the control groups all mice died within 40 to 50 days, 40% of bsAb treated animals survived longer than 60 days. Our preclinical results suggest that bsAb FabCD19xdsFvCD5 may evolve as a promising novel reagent that is worth investigating in early clinical trials for thus far incurable B-cell lymphoma patients.
Last update: 23 November 2012