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

Fransson, Johan LU and Borrebaeck, Carl LU (2006) In International Journal of Cancer 119(10). p.2492-2496
Abstract
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... (More)
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. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
human antibody, phage display, Ku heterodimer, internalizing, immunotherapy
in
International Journal of Cancer
volume
119
issue
10
pages
2492 - 2496
publisher
John Wiley and Sons
external identifiers
  • wos:000241222300036
  • pmid:16929494
  • scopus:33749590001
ISSN
0020-7136
DOI
10.1002/ijc.22212
language
English
LU publication?
yes
id
501c88fa-7c76-4dbb-9fe5-abbbd357eadd (old id 388067)
date added to LUP
2016-04-01 11:47:04
date last changed
2021-09-29 05:20:50
@article{501c88fa-7c76-4dbb-9fe5-abbbd357eadd,
  abstract     = {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.},
  author       = {Fransson, Johan and Borrebaeck, Carl},
  issn         = {0020-7136},
  language     = {eng},
  number       = {10},
  pages        = {2492--2496},
  publisher    = {John Wiley and Sons},
  series       = {International Journal of Cancer},
  title        = {The nuclear DNA repair protein Ku70/80 is a tumor-associated antigen displaying rapid receptor mediated endocytosis},
  url          = {http://dx.doi.org/10.1002/ijc.22212},
  doi          = {10.1002/ijc.22212},
  volume       = {119},
  year         = {2006},
}