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The nuclear DNA repair protein Ku70/80 is a tumor-associated antigen displaying rapid receptor mediated endocytosis

Author:
  • Johan Fransson
  • Carl Borrebaeck
Publishing year: 2006
Language: English
Pages: 2492-2496
Publication/Series: International Journal of Cancer
Volume: 119
Issue: 10
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

To be of therapeutic relevance, a tumor-associated antigen should be expressed on the surface of neoplastic cells but not, or to a significantly lower extent, on cells of non-transformed nature. The Ku heterodimer (Ku70/80) is involved in DNA double strand break recognition and repair and is ubiquitously expressed in the nucleus of all cells. However, its exclusive nuclear localization has been reassessed by studies that demonstrate Ku to be expressed on the surface of tumor cell lines, displaying functions in cell adhesion, migration and invasion. In this study, we add another feature to the pluripotent role of Ku70/80 by showing that, upon binding the novel human recombinant antibody INCA-X, the Ku70/80 heterodimer is internalized into pancreatic carcinoma cells. The receptor-mediated endocytosis of Ku70/80 is rapid (t(1/2) 12 min) and extensive (90% of the receptor pool inside the cell after 100 min) as measured by rotating radioimmunoassay. Ku70/80 was also successfully used as a port of entry for cytotoxic payloads to tumor cells of various origin, as determined by indirect inummotoxin administration of a saporin-conjugated, secondary anti-human antibody. Thus, the internalization properties of the Ku70/80 suggest a potential role of this tumor associated antigen in selective drug-delivery in several human malignancies. (c) 2006 Wiley-Liss, Inc.

Keywords

  • Cancer and Oncology
  • human antibody
  • phage display
  • Ku heterodimer
  • internalizing
  • immunotherapy

Other

Published
  • ISSN: 0020-7136
Carl Borrebaeck
E-mail: carl [dot] borrebaeck [at] immun [dot] lth [dot] se

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Department of Immunotechnology

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