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 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. © 2015 heublein et al.; licensee biomed central.