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

• Published in: Journal of experimental & clinical cancer research 2015-05, Vol.34 (1), p.50-50, Article 50
• Main Authors: Heublein, Sabine, Mayr, Doris, Egger, Markus, Karsten, Uwe, Goletz, Steffen, Angele, Martin, Gallwas, Julia, Jeschke, Udo, Ditsch, Nina
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Antibodies; Antibodies, Monoclonal, Humanized - immunology; Antibodies, Monoclonal, Humanized - therapeutic use; Antigenic determinants; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Antineoplastic Agents - immunology; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor; Biopharmaceutics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer patients; Care and treatment; Disease susceptibility; Epitopes - immunology; Female; Genetic aspects; Health aspects; Humans; Immunohistochemistry; Middle Aged; Mucin-1 - immunology; Mucin-1 - metabolism; Mucins; Neoplasm Grading; Prognosis; Survival Analysis; Viral antibodies
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-015-0152-7

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. 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. 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. 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.