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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/3910

Title: TARGETING OF TUMOR-NECROSIS-FACTOR TO TUMOR-CELLS - SECRETION BY MYELOMA CELLS OF A GENETICALLY ENGINEERED ANTIBODY-TUMOR NECROSIS FACTOR HYBRID MOLECULE
Authors: HOOGENBOOM, HR
RAUS, Jef
VOLCKAERT, G
Issue Date: 1991
Publisher: ELSEVIER SCIENCE BV
Citation: BIOCHIMICA ET BIOPHYSICA ACTA, 1096(4). p. 345-354
Abstract: The construction, synthesis and secretion of a genetically engineered antibody-cytokine fusion molecule is described. To target tumor necrosis factor (TNF) to tumor cells, recombinant antibody techniques were used to produce a Fab-like antibody-TNF conjugate. At the gene level, the heavy chain gene of an antitransferrin receptor antibody was linked to a synthetic TNF gene encoding human TNF. Transfection of the heavy chain-TNF gene into a myeloma derived cell line which was producing the light chain of the same antibody, allowed the isolation of a cell line secreting a fusion protein of the expected molecular weight and composition. The culture supernatant of the cell line contained TNF cytotoxic activity towards murine L929 cells and human MCF-7 cells. Cytotoxicity towards the human cancer cells was inhibited by an excess of the original antitransferrin receptor antibody, indicating that the antibody-TNF molecules are targeted to the transferrin receptor rich tumor cells. Since the antibody genes used are chimeric (i.e. composed of mouse variable and human constant regions) and since DNA encoding human TNF was used, the hybrid protein is an example of a humanized immunotoxin-like molecule. These results illustrate the possibilities of antibody engineering technology to create and produce improved agents for cancer therapy. Furthermore, they demonstrate for the first time the ability of myeloma cells to secrete an antibody-cytokine chimeric molecule.
Notes: LIMBURGS UNIV CENTRUM,DR L WILLEMS INST,DEPT WNIF,UNIV CAMPUS,B-3610 DIEPENBEEK,BELGIUM. CATHOLIC UNIV LEUVEN,GENTECHNOL LAB,B-3000 LOUVAIN,BELGIUM.
URI: http://hdl.handle.net/1942/3910
DOI: 10.1016/0925-4439(91)90071-G
ISI #: A1991FT98800011
ISSN: 0006-3002
Type: Journal Contribution
Appears in Collections: Research publications

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