Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor Immunotherapy

Abstract Trifunctional bispecific antibodies (trAbs) used in tumor immunotherapy have the unique ability to recruit T cells toward antigens on the tumor cell surface and, moreover, to activate accessory cells through their immunoglobulin Fc region interacting with activating Fcγ receptors. This scen...

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Main Authors: Nina Eissler, Josef Mysliwietz, Nina Deppisch, Peter Ruf, Horst Lindhofer, Ralph Mocikat
Format: Article
Language:English
Published: BMC 2013-03-01
Series:Molecular Medicine
Subjects:
Online Access:https://doi.org/10.2119/molmed.2012.00140
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author Nina Eissler
Josef Mysliwietz
Nina Deppisch
Peter Ruf
Horst Lindhofer
Ralph Mocikat
author_facet Nina Eissler
Josef Mysliwietz
Nina Deppisch
Peter Ruf
Horst Lindhofer
Ralph Mocikat
author_sort Nina Eissler
collection DOAJ
description Abstract Trifunctional bispecific antibodies (trAbs) used in tumor immunotherapy have the unique ability to recruit T cells toward antigens on the tumor cell surface and, moreover, to activate accessory cells through their immunoglobulin Fc region interacting with activating Fcγ receptors. This scenario gives rise to additional costimulatory signals required for T cell-mediated tumor cell destruction and induction of an immunologic memory. Here we show in an in vitro system that most effective trAb-dependent T-cell activation and tumor cell elimination are achieved in the presence of dendritic cells (DCs). On the basis of these findings, we devise a novel approach of cancer immunotherapy that combines the specific advantages of trAbs with those of DC-based vaccination. Simultaneous delivery of trAbs and in vitro differentiated DCs resulted in a markedly improved tumor rejection in a murine melanoma model compared with monotherapy.
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spelling doaj.art-08ec4f4b1668430db55894883c0eab702023-08-06T11:17:45ZengBMCMolecular Medicine1076-15511528-36582013-03-01191546110.2119/molmed.2012.00140Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor ImmunotherapyNina Eissler0Josef Mysliwietz1Nina Deppisch2Peter Ruf3Horst Lindhofer4Ralph Mocikat5Institut für Molekulare Immunologie, Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und UmweltInstitut für Molekulare Immunologie, Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und UmweltInstitut für Molekulare Immunologie, Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und UmweltTrion ResearchTrion ResearchInstitut für Molekulare Immunologie, Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und UmweltAbstract Trifunctional bispecific antibodies (trAbs) used in tumor immunotherapy have the unique ability to recruit T cells toward antigens on the tumor cell surface and, moreover, to activate accessory cells through their immunoglobulin Fc region interacting with activating Fcγ receptors. This scenario gives rise to additional costimulatory signals required for T cell-mediated tumor cell destruction and induction of an immunologic memory. Here we show in an in vitro system that most effective trAb-dependent T-cell activation and tumor cell elimination are achieved in the presence of dendritic cells (DCs). On the basis of these findings, we devise a novel approach of cancer immunotherapy that combines the specific advantages of trAbs with those of DC-based vaccination. Simultaneous delivery of trAbs and in vitro differentiated DCs resulted in a markedly improved tumor rejection in a murine melanoma model compared with monotherapy.https://doi.org/10.2119/molmed.2012.00140Trifunctional Bispecific AntibodyFACS StainingInduce Tumor Cell KillingCatumaxomabKill Tumor Cells
spellingShingle Nina Eissler
Josef Mysliwietz
Nina Deppisch
Peter Ruf
Horst Lindhofer
Ralph Mocikat
Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor Immunotherapy
Molecular Medicine
Trifunctional Bispecific Antibody
FACS Staining
Induce Tumor Cell Killing
Catumaxomab
Kill Tumor Cells
title Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor Immunotherapy
title_full Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor Immunotherapy
title_fullStr Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor Immunotherapy
title_full_unstemmed Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor Immunotherapy
title_short Potential of the Trifunctional Bispecific Antibody Surek Depends on Dendritic Cells: Rationale for a New Approach of Tumor Immunotherapy
title_sort potential of the trifunctional bispecific antibody surek depends on dendritic cells rationale for a new approach of tumor immunotherapy
topic Trifunctional Bispecific Antibody
FACS Staining
Induce Tumor Cell Killing
Catumaxomab
Kill Tumor Cells
url https://doi.org/10.2119/molmed.2012.00140
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