| Efficacy of catumaxomab in tumor spheroid killing is mediated by its trifunctional mode of action. | |
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MedLine Citation:
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PMID: 20652245 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Catumaxomab is an intact trifunctional bispecific antibody targeting human EpCAM (epithelial cell adhesion molecule) and CD3 with further binding to Fcgamma receptor type I, IIa and III. We choose multicellular tumor spheroids (MCTS) of human EpCAM-positive FaDu tumor cells in co-culture with human peripheral blood mononuclear cells as an adequate three-dimensional in vitro model for pharmacological testing of catumaxomab. We found a strong dose-dependent antitumor response mediated by catumaxomab, with volume-decreased or completely destroyed tumor spheroids together with a massive immune cell infiltration and decreased signals for cancer cell viability and clonogenicity. In control experiments with F(ab')2 fragments of catumaxomab and the parental antibodies alone or in combination the effects in spheroid volume reduction were less than that of catumaxomab. All binding partners of the postulated tricell complex have to be present to exert catumaxomab's full mode of action. These distinct effects of catumaxomab are based on the unique composition of the trifunctional bispecific antibody. Since, in general, many cancers are treated by chemotherapy in combination with immunological tumor therapy, we additionally analyzed the effects of cisplatin alone and in combination with catumaxomab. For cisplatin alone we detected a dose-dependent response relating to decrease of spheroid volume. The combined approach resulted in a synergistic spheroid volume decrease and the colony formation was reduced to non-detectable levels. |
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Authors:
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Franziska Hirschhaeuser; Stefan Walenta; Wolfgang Mueller-Klieser |
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Publication Detail:
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Type: Journal Article Date: 2010-07-21 |
Journal Detail:
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Title: Cancer immunology, immunotherapy : CII Volume: 59 ISSN: 1432-0851 ISO Abbreviation: Cancer Immunol. Immunother. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-08-30 Completed Date: 2010-09-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8605732 Medline TA: Cancer Immunol Immunother Country: Germany |
Other Details:
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Languages: eng Pagination: 1675-84 Citation Subset: IM |
Affiliation:
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Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Bispecific
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therapeutic use* Antigens, CD3 / immunology* Antigens, Neoplasm / immunology* Antineoplastic Agents / therapeutic use Carcinoma, Squamous Cell / immunology, therapy* Cell Adhesion Molecules / immunology* Cell Survival Cisplatin / therapeutic use Coculture Techniques Combined Modality Therapy Head and Neck Neoplasms / immunology, therapy* Humans Immunotherapy* Spheroids, Cellular / immunology, pathology* Tumor Cells, Cultured Tumor Stem Cell Assay |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Bispecific; 0/Antigens, CD3; 0/Antigens, Neoplasm; 0/Antineoplastic Agents; 0/Cell Adhesion Molecules; 0/catumaxomab; 0/tumor-associated antigen GA733; 15663-27-1/Cisplatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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