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

Journal of Experimental & Clinical Cancer Research

Nina Ditsch³  Udo Jeschke³  Julia Gallwas³  Martin Angele²  Steffen Goletz⁴  Uwe Karsten⁴  Markus Egger³  Doris Mayr¹  Sabine Heublein³ 

[1] Department of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany;Department of Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany;Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, Munich, 81377, Germany;Glycotope GmbH, Berlin-Buch, Germany

关键词: Immunohistochemistry;    TA-MUC1;    MUC1;    Breast cancer;    Prognosis;    PankoMab-GEX™;   

Others  :  1220698
DOI  :  10.1186/s13046-015-0152-7

 received in 2014-12-03, accepted in 2015-04-01,  发布年份 2015

【 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.

【 授权许可】

   
2015 Heublein et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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