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

摘要

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.