Sabine Heublein1,2, Klaus Friese3,4, Bernd Kost3, Frederik Marmé5, Christina Kuhn3, Sven Mahner3,6, Christian Dannecker3,6, Doris Mayr7, Udo Jeschke3, Aurelia Vattai3. 1. Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University of Munich, Maistrasse 11, 80337, Munich, Germany. sabine.heublein@med.uni-heidelberg.de. 2. Department of Obstetrics and Gynecology, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. sabine.heublein@med.uni-heidelberg.de. 3. Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University of Munich, Maistrasse 11, 80337, Munich, Germany. 4. Department of Gynaecologic Oncology, Bad Trissl, Bad-Trissl-Str. 73, 83080, Oberaudorf, Germany. 5. Department of Obstetrics and Gynecology, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. 6. Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, Marachioninistraße 15, 81375, Heidelberg, Germany. 7. Department of Pathology, Klinikum der Universität München, Ludwig-Maximilians University of Munich, Thalkirchner Str. 36, 80337, Munich, Germany.
Abstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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). METHODS: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. RESULTS: 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 cancerpatients with exceptional short RFS and OS. CONCLUSIONS: 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.
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