title: Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients.
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.
authors.affiliation: Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. sabine.heublein@med.uni-muenchen.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Heublein
authors.affiliation: Department of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany. doris.mayr@med.uni-muenchen.de.
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.affiliation: Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. e_markus@gmx.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Egger
authors.affiliation: Glycotope GmbH, Berlin-Buch, Germany. uwe.karsten@glycotope.com.
authors.forename: Uwe
authors.initials: U
authors.lastname: Karsten
authors.affiliation: Glycotope GmbH, Berlin-Buch, Germany. steffen.goletz@glycotope.com.
authors.forename: Steffen
authors.initials: S
authors.lastname: Goletz
authors.affiliation: Department of Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany. martin.angele@med.uni-muenchen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Angele
authors.affiliation: Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. julia.gallwas@med.uni-muenchen.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Gallwas
authors.affiliation: Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. udo.jeschke@med.uni-muenchen.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
authors.affiliation: Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. nina.ditsch@med.uni-muenchen.de.
authors.forename: Nina
authors.initials: N
authors.lastname: Ditsch
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology / Q000378:metabolism; D060787:Neoplasm Grading; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000939:Epitopes; D018396:Mucin-1; C581698:PankoMab-GEX