Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: Fusion of the toxin moiety to the scFv did neither affect its thermal stability nor its antigen-binding affinity. In vitro, 4D5MOCB-ETA potently and specifically inhibited protein synthesis and reduced the viability of Ep-CAM-positive carcinoma cells of diverse histological origins with IC(50)s ranging from 0.005 to 0.2 pM. Upon systemic administration in mice, 4D5MOCB-ETA showed similar organ distribution as the scFv 4D5MOCB and preferentially localized to Ep-CAM-positive tumor xenografts with a tumor:blood ratio of 5.4. The potent antitumor activity of 4D5MOCB-ETA was demonstrated by its ability to strongly inhibit the growth and induce regression of relatively large tumor xenografts derived from lung, colon, or squamous cell carcinomas. CONCLUSIONS:
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Authors | Claudio Di Paolo, Jörg Willuda, Susanne Kubetzko, Ikar Lauffer, Dominique Tschudi, Robert Waibel, Andreas Plückthun, Rolf A Stahel, Uwe Zangemeister-Wittke |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 9
Issue 7
Pg. 2837-48
(Jul 2003)
ISSN: 1078-0432 [Print] United States |
PMID | 12855664
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Bacterial Toxins
- Cell Adhesion Molecules
- Exotoxins
- Immunoglobulin Fragments
- Immunotoxins
- Recombinant Proteins
- Virulence Factors
- immunotoxin 4D5MOCB-ETA
- ADP Ribose Transferases
- Pseudomonas aeruginosa exotoxin A
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Topics |
- ADP Ribose Transferases
(chemistry)
- Animals
- Antineoplastic Agents
(pharmacology)
- Bacterial Toxins
(chemistry, pharmacology)
- Cell Adhesion Molecules
- Cell Division
- Cell Line, Tumor
- Chromatography, Gel
- Dose-Response Relationship, Drug
- Epithelial Cells
(metabolism)
- Exotoxins
(chemistry)
- Female
- Flow Cytometry
- Genetic Vectors
- Humans
- Immunoglobulin Fragments
(chemistry, pharmacology)
- Immunotoxins
(pharmacology)
- Inhibitory Concentration 50
- Mice
- Mice, Inbred C57BL
- Mice, Nude
- Models, Molecular
- Neoplasm Transplantation
- Protein Structure, Tertiary
- Recombinant Proteins
(pharmacology)
- Time Factors
- Virulence Factors
(chemistry)
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