The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-07

AUTHORS

R Zeidler, J Mysliwietz, M Csánady, A Walz, I Ziegler, B Schmitt, B Wollenberg, H Lindhofer

ABSTRACT

Bispecific antibodies (bsAb) are considered as promising tools for the elimination of disseminated tumour cells in a minimal residual disease situation. The bsAb-mediated recruitment of an immune effector cell in close vicinity of a tumour cell is thought to induce an antitumoural immune response. However, classical bispecific molecules activate only a single class of immune effector cell that may not yield optimal immune responses. We therefore constructed an intact bispecific antibody, BiUII (anti-CD3 x anti-EpCAM), that not only recognizes tumour cells and T lymphocytes with its two binding arms, but also binds and activates Fcgamma-receptor positive accessory cells through its Fc-region. We have demonstrated recently that activated accessory cells contribute to the bsAb-induced antitumoural activity. We now analyse this stimulation in more detail and demonstrate here the BiUII-induced upregulation of activation markers like CD83 and CD95 on accessory cells and the induction of neopterin and biopterin synthesis. Experiments with pure cell subpopulations revealed binding of BiUII to CD64+ accessory cells and CD16+ NK cells, but not to CD32+ B lymphocytes. We provide further evidence for the importance of the Fc-region in that this bispecific molecule stimulates Fcgamma-R-positive accessory cells to eliminate tumour cells in vitro by direct phagocytosis. More... »

PAGES

261-266

Journal

TITLE

British Journal of Cancer

ISSUE

2

VOLUME

83

Clinical Trials linked to this publication

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  • An Open-Label, Single-Arm, Phase Ii Safety And Tolerability Study Of Catumaxomab (Anti-Epcam X Anti-Cd3) In Women With Advanced Epithelial Ovarian Cancer After A Complete Response To Chemotherapy
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  • Phase Ii Open Label Study To Evaluate The Safety Of A Second I.P. Infusion Cycle Of Catumaxomab In Patients With Malignant Ascites Due To Carcinoma, Requiring Their First Therapeutic Puncture After Treatment In The Casimas Study
  • Multicenter, Open-Label Phase Ii Study To Evaluate The Safety And Efficacy Of The Trifunctional Bispecific Antibody Catumaxomab (Anti-Epcam X Anti-Cd3) In Patients With Gastric Adenocarcinoma After Neoadjuvant Chemotherapy And Intended Curative Resection
  • Phase Ii Study Of The Trifunctional Bispecific Anti-Her-2/Neu X Anti-Cd3 Antibody Ertumaxomab In Patients With Her-2/Neu Overexpressing (3+ Or 2+/Fish+) Metastatic Breast Cancer Progressing After Trastuzumab Treatment
  • Multicenter, Open-Label And Randomized Phase Ii Study To Evaluate Safety And Efficacy Of The Trifunctional Bispecific Antibody Catumaxomab (Anti-Epcam X Anti-Cd3) In Patients After Curative Resection Of A Confirmed Gastric Adenocarcinoma Compared With Surgery Alone
  • Two-Arm, Randomized (2:1), Open-Label Phase Ii/Iii Study In Epcam Positive Cancer Patients With Symptomatic Malignant Ascites Using The Trifuncitonal Bispecific Antibody Removab (Anti-Epcam X Anti-Cd3) Versus An Untreated Control Group
  • Phase Ii Study Of The Trifunctional Anti-Her-2/Neu X Anti-Cd3 Antibody Ertumaxomab For Hormone Therapy Refractory Patients With Her-2/Neu 1+ Or 2+ Expressing Advanced Or Metastatic Breast Cancer
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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1054/bjoc.2000.1237

    DOI

    http://dx.doi.org/10.1054/bjoc.2000.1237

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10901380


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