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Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients
BACKGROUND: Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly expressed epithelial cell surface antigen and has evolved to be the most predictive serum tumour marker in breast cancer. PankoMab-GEX™, which is currently being evaluated for its therapeutic efficacy in a phase IIb cli...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447018/ https://www.ncbi.nlm.nih.gov/pubmed/25986064 http://dx.doi.org/10.1186/s13046-015-0152-7 |
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author | Heublein, Sabine Mayr, Doris Egger, Markus Karsten, Uwe Goletz, Steffen Angele, Martin Gallwas, Julia Jeschke, Udo Ditsch, Nina |
author_facet | Heublein, Sabine Mayr, Doris Egger, Markus Karsten, Uwe Goletz, Steffen Angele, Martin Gallwas, Julia Jeschke, Udo Ditsch, Nina |
author_sort | Heublein, Sabine |
collection | PubMed |
description | BACKGROUND: Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly expressed epithelial cell surface antigen and has evolved to be the most predictive serum tumour marker in breast cancer. PankoMab-GEX™, which is currently being evaluated for its therapeutic efficacy in a phase IIb clinical trial, is a glyco-optimized anti-MUC1 antibody specifically recognizing a tumour-associated MUC1 epitope (TA-MUC1). The current study aimed to analyse the immunoreactivity of PankoMabGEX™ and its correlation with established clinico-pathological variables including 10-year and overall survival in a large cohort of breast cancer patients. METHODS: Breast cancer tissue sections (n = 227) underwent a standardized immunohistochemical staining protocol for TA-MUC1 by using PankoMab-GEX™ as a primary antibody. The staining was evaluated by two independent observers and quantified by applying the IR-score. RESULTS: TA-MUC1 as detected by PankoMab-GEX™ was identified in 74.9% of breast cancer tissue sections. Patients were subdivided according to the subcellular localisation of TA-MUC1 and cases classified as mem-PankoMab-GEX™ (solely membranous) positive, cyt-PankoMab-GEX™ (solely cytoplasmic) positive, double positive or as completely negative were compared regarding their survival. Herein mem-PankoMab-GEX™-positive patients performed best, while double-negative ones presented with a significantly shortened survival. Positivity for mem-PankoMab-GEX™ as well as a double-negative immunophenotype turned out to be independent prognosticators for survival. CONCLUSIONS: This is the first study to report on PankoMab-GEX™ in a large panel of breast cancer patients. The PankoMab-GEX™ epitope TA-MUC1 could be identified in the majority of cases and was found to be an independent prognosticator depending on its subcellular localisation. Since TA-MUC1 is known to be highly immunogenic cancers staining positive for PankoMab-GEX™ might be more compromised by host anti-tumour immune defence. Further, the observations reported here might be fundamental for selecting patients to undergo PankoMab-GEX™-containing chemotherapy protocols. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-015-0152-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4447018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44470182015-05-29 Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients Heublein, Sabine Mayr, Doris Egger, Markus Karsten, Uwe Goletz, Steffen Angele, Martin Gallwas, Julia Jeschke, Udo Ditsch, Nina J Exp Clin Cancer Res Research Article BACKGROUND: Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly expressed epithelial cell surface antigen and has evolved to be the most predictive serum tumour marker in breast cancer. PankoMab-GEX™, which is currently being evaluated for its therapeutic efficacy in a phase IIb clinical trial, is a glyco-optimized anti-MUC1 antibody specifically recognizing a tumour-associated MUC1 epitope (TA-MUC1). The current study aimed to analyse the immunoreactivity of PankoMabGEX™ and its correlation with established clinico-pathological variables including 10-year and overall survival in a large cohort of breast cancer patients. METHODS: Breast cancer tissue sections (n = 227) underwent a standardized immunohistochemical staining protocol for TA-MUC1 by using PankoMab-GEX™ as a primary antibody. The staining was evaluated by two independent observers and quantified by applying the IR-score. RESULTS: TA-MUC1 as detected by PankoMab-GEX™ was identified in 74.9% of breast cancer tissue sections. Patients were subdivided according to the subcellular localisation of TA-MUC1 and cases classified as mem-PankoMab-GEX™ (solely membranous) positive, cyt-PankoMab-GEX™ (solely cytoplasmic) positive, double positive or as completely negative were compared regarding their survival. Herein mem-PankoMab-GEX™-positive patients performed best, while double-negative ones presented with a significantly shortened survival. Positivity for mem-PankoMab-GEX™ as well as a double-negative immunophenotype turned out to be independent prognosticators for survival. CONCLUSIONS: This is the first study to report on PankoMab-GEX™ in a large panel of breast cancer patients. The PankoMab-GEX™ epitope TA-MUC1 could be identified in the majority of cases and was found to be an independent prognosticator depending on its subcellular localisation. Since TA-MUC1 is known to be highly immunogenic cancers staining positive for PankoMab-GEX™ might be more compromised by host anti-tumour immune defence. Further, the observations reported here might be fundamental for selecting patients to undergo PankoMab-GEX™-containing chemotherapy protocols. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-015-0152-7) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-19 /pmc/articles/PMC4447018/ /pubmed/25986064 http://dx.doi.org/10.1186/s13046-015-0152-7 Text en © Heublein et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Heublein, Sabine Mayr, Doris Egger, Markus Karsten, Uwe Goletz, Steffen Angele, Martin Gallwas, Julia Jeschke, Udo Ditsch, Nina Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients |
title | Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients |
title_full | Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients |
title_fullStr | Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients |
title_full_unstemmed | Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients |
title_short | Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients |
title_sort | immunoreactivity of the fully humanized therapeutic antibody pankomab-gex™ is an independent prognostic marker for breast cancer patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447018/ https://www.ncbi.nlm.nih.gov/pubmed/25986064 http://dx.doi.org/10.1186/s13046-015-0152-7 |
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