Cited by 18Breast Cancer Treatment StudiesMonoclonal and Polyclonal Antibodies ResearchHER2/EGFR in Cancer Research

Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients

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Heublein, Sabine, Mayr, Doris, Egger, Markus, Karsten, Uwe, Goletz, Steffen, Angele, Martin, Gallwas, Julia, Jeschke, Udo +1 more·2015·Journal of Experimental & Clinical Cancer Research

Abstract

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.

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  • MUC1 is overexpressed on some adenocarcinoma cells and is an important tumor surface marker, especially for breast cancer.

    “MUC1 is a mucin glycoprotein overexpressed on some adenocarcinoma cells and is considered an important tumor surface marker, especially breast cancer. It has been used as a potential target for the treatment of breast cancer.250,251”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [251]

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Authors
Heublein, S., Mayr, D., Egger, M., Karsten, U., Goletz, S., Angele, M., Gallwas, J., Jeschke, U., & Ditsch, N.
Affiliations
  • Ludwig-Maximilians-Universität München (DE)
  • Pathologisches Institut (DE)
  • Glycotope (Germany) (DE)
Corresponding author
Heublein, Sabine
Venue
Journal of Experimental & Clinical Cancer Research
Published
2015-05-19
Volume
34
Issue
1
Pages
50-50
ISSN
  • 0392-9078 (ISSN-L)
  • 1756-9966
OpenAlex
W2115902453
Cited by
18
References
33
Citations by year
2026: 1 · 2025: 2 · 2023: 2 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2
FWCI
0.44
Type
journal article
Language
en
Open access
Locations
  • Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords
MUC1, CA15-3, breast cancer, prognostic factors, therapeutic antibodies, subcellular localization, immunoreactivity score, overall survival, patient selection for chemotherapy, antitumor immunity
MeSH terms
Adult, Aged, Epitopes, Antigens, Neoplasm, Antineoplastic Agents, Breast Neoplasms, Female, Humans, Middle Aged, Prognosis, Biomarkers, Tumor, Survival Analysis, Mucin-1, Neoplasm Grading, Antibodies, Monoclonal, Humanized

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