The nuclear DNA repair protein Ku70/80 is a tumor-associated antigen displaying rapid receptor mediated endocytosis
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/388067
- author
- Fransson, Johan LU and Borrebaeck, Carl LU
- organization
- publishing date
- 2006
- 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 & Sons Inc.
- 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
- 2022-01-26 18:13:25
@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}},
keywords = {{human antibody; phage display; Ku heterodimer; internalizing; immunotherapy}},
language = {{eng}},
number = {{10}},
pages = {{2492--2496}},
publisher = {{John Wiley & Sons Inc.}},
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}},
}