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Heublein, Sabine; Friese, Klaus; Kost, Bernd; Marme, Frederik; Kuhn, Christina; Mahner, Sven; Dannecker, Christian; Mayr, Doris; Jeschke, Udo; Vattai, Aurelia (2018): TA-MUC1 as detected by the fully humanized, therapeutic antibody Gatipotzumab predicts poor prognosis in cervical cancer. In: Journal of Cancer Research and Clinical Oncology, Vol. 144, No. 10: pp. 1899-1907
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Abstract

Gatipotuzumab is a fully humanized antibody which was designed to detect a cancer-specific glyco-modification of MUC1 (termed 'TA-MUC1') and which was optimized to effectively trigger antibody-dependent-cell-mediated cytotoxicity (ADCC) in cancer cells. Clinical trials investigating therapeutic efficacy of this antibody have been published recently. The current analysis aimed to determine whether TA-MUC1-as detected by Gatipotuzumab-is expressed in cervical cancer tissue and whether binding of Gatipotuzumab is associated with clinico-pathological variables including recurrence free (RFS) and overall survival (OS). Cervical cancer tissue (n = 250) was stained for TA-MUC1 using Gatipotuzumab employing a standardized immunohistochemistry protocol. Staining was scored by applying the IR-score. Results were binarized and tested for association to clinico-pathological parameters. TA-MUC1 as stained by Gatipotuzumab was detected in 188 (75.2%) out of the 250 cervical cancer cases investigated. Expression of TA-MUC1 was restricted to cancer cells and was positively correlated with viral oncoprotein E6. Membrane staining of TA-MUC1 predicted significantly reduced RFS and OS. Importantly, expression of TA-MUC1 at the cell surface identified a group of early stage cervical cancer patients with exceptional short RFS and OS. We report TA-MUC1-the antigen detected by Gatipotzumab-to be widely expressed in cervical cancer tissue and to localize to the cell membrane. The latter is seen as a pre-requisite to target this epitope by antibody-drug conjugates or antibodies eliciting ADCC. Since especially, membrane localization of TA-MUC1 predicted poor prognosis, evaluating Gatipotuzumab for its therapeutic efficacy in cervical cancer may turn attractive.