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Molecular evolution of specific human antibody against MUC1 mucin results in improved recognition of the antigen on tumour cells

Persson, Jonas LU ; Bäckström, Malin; Johansson, Henrik; Jirström, Karin LU ; Hansson, Gunnar C. and Ohlin, Mats LU (2009) In Tumor Biology 30(4). p.221-231
Abstract
The MUC1 mucin is differentially expressed and glycosylated in cancer tissue as opposed to healthy tissue. Due to these differences, MUC1 is considered a potential biomarker suitable for cancer diagnosis and therapy. In a previous study, the human MUC1-specific antibody 12ESC-6 was able to bind a sequence variant of the tandem repeat of MUC1 that is not recognized by many other MUC1-specific antibodies. It was also found to bind efficiently to MUC1-carrying cells. We have now used 12ESC-6 as starting point for random mutagenesis to isolate variants with improved ability to bind MUC1 in human tumor tissue. The resulting 12ESC-6 variants were shown to recognize not only the naked MUC1 tandem repeat but even more so glycosylated variants... (More)
The MUC1 mucin is differentially expressed and glycosylated in cancer tissue as opposed to healthy tissue. Due to these differences, MUC1 is considered a potential biomarker suitable for cancer diagnosis and therapy. In a previous study, the human MUC1-specific antibody 12ESC-6 was able to bind a sequence variant of the tandem repeat of MUC1 that is not recognized by many other MUC1-specific antibodies. It was also found to bind efficiently to MUC1-carrying cells. We have now used 12ESC-6 as starting point for random mutagenesis to isolate variants with improved ability to bind MUC1 in human tumor tissue. The resulting 12ESC-6 variants were shown to recognize not only the naked MUC1 tandem repeat but even more so glycosylated variants thereof, in particular those carrying the GalNAc (Tn) glycoform. Selected variants of 12ESC-6 demonstrated improved staining of MUC1 on cell lines using flow cytometry and improved staining of the antigen in breast tumor tissue by immunohistochemistry. Molecular evolution and specific fine-tuning thus have the potential to improve the performance of antibody specificities targeting tumor-associated epitopes on MUC1 mucin. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Tumor Biology
volume
30
issue
4
pages
221 - 231
publisher
Springer
external identifiers
  • wos:000270063500007
  • scopus:70349250523
ISSN
1423-0380
DOI
10.1159/000240634
project
CREATE Health
language
English
LU publication?
yes
id
a0d6e67f-90b4-47e6-a0f5-0ee3289b28fd (old id 1438914)
date added to LUP
2009-08-03 13:46:22
date last changed
2017-07-09 04:08:33
@article{a0d6e67f-90b4-47e6-a0f5-0ee3289b28fd,
  abstract     = {The MUC1 mucin is differentially expressed and glycosylated in cancer tissue as opposed to healthy tissue. Due to these differences, MUC1 is considered a potential biomarker suitable for cancer diagnosis and therapy. In a previous study, the human MUC1-specific antibody 12ESC-6 was able to bind a sequence variant of the tandem repeat of MUC1 that is not recognized by many other MUC1-specific antibodies. It was also found to bind efficiently to MUC1-carrying cells. We have now used 12ESC-6 as starting point for random mutagenesis to isolate variants with improved ability to bind MUC1 in human tumor tissue. The resulting 12ESC-6 variants were shown to recognize not only the naked MUC1 tandem repeat but even more so glycosylated variants thereof, in particular those carrying the GalNAc (Tn) glycoform. Selected variants of 12ESC-6 demonstrated improved staining of MUC1 on cell lines using flow cytometry and improved staining of the antigen in breast tumor tissue by immunohistochemistry. Molecular evolution and specific fine-tuning thus have the potential to improve the performance of antibody specificities targeting tumor-associated epitopes on MUC1 mucin.},
  author       = {Persson, Jonas and Bäckström, Malin and Johansson, Henrik and Jirström, Karin and Hansson, Gunnar C. and Ohlin, Mats},
  issn         = {1423-0380},
  language     = {eng},
  number       = {4},
  pages        = {221--231},
  publisher    = {Springer},
  series       = {Tumor Biology},
  title        = {Molecular evolution of specific human antibody against MUC1 mucin results in improved recognition of the antigen on tumour cells},
  url          = {http://dx.doi.org/10.1159/000240634},
  volume       = {30},
  year         = {2009},
}