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Carl B

Carl Borrebaeck

Professor

Carl B

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

Author

  • Johan Fransson
  • Carl Borrebaeck

Summary, in 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.

Department/s

  • Department of Immunotechnology

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 Inc.

Topic

  • Cancer and Oncology

Keywords

  • human antibody
  • phage display
  • Ku heterodimer
  • internalizing
  • immunotherapy

Status

Published

ISBN/ISSN/Other

  • ISSN: 0020-7136