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Journal of Cancer Research and Clinical Oncology

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30.07.2018 | Original Article–Cancer Research

TA-MUC1 as detected by the fully humanized, therapeutic antibody Gatipotzumab predicts poor prognosis in cervical cancer

verfasst von: Sabine Heublein, Klaus Friese, Bernd Kost, Frederik Marmé, Christina Kuhn, Sven Mahner, Christian Dannecker, Doris Mayr, Udo Jeschke, Aurelia Vattai

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2018

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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.

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Titel: TA-MUC1 as detected by the fully humanized, therapeutic antibody Gatipotzumab predicts poor prognosis in cervical cancer
verfasst von: Sabine Heublein
Klaus Friese
Bernd Kost
Frederik Marmé
Christina Kuhn
Sven Mahner
Christian Dannecker
Doris Mayr
Udo Jeschke
Aurelia Vattai
Publikationsdatum: 30.07.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2018
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2706-5

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TA-MUC1 as detected by the fully humanized, therapeutic antibody Gatipotzumab predicts poor prognosis in cervical cancer

Abstract

Background

Methods

Results

Conclusions

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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Abstract

Background

Methods

Results

Conclusions

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