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Mesothelin as a target for cervical cancer therapy

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The cell surface glycoprotein Mesothelin is overexpressed in several tumor entities and novel immune-based therapies are currently under the early clinical evaluation for the treatment of malignant pleura mesothelioma, ovarian cancer, and pancreatic cancer. Cervical cancer has not been recognized as a suitable target for Mesothelin-directed immune therapies so far.

Methods

To exploit a possible role of Mesothelin in cervical cancer treatment, we analysed Mesothelin expression in 79 cervical carcinomas and aligned expressions patterns with tumor growth parameters. A novel anti-Mesothelin drug conjugate (Anetumab Ravtansine) was applied for dose-efficiency studies in a Mesothelin positive tumor model for cervical cancer in Scid mice.

Results

In more than three-quarters (77%) of cervical adenocarcinomas, Mesothelin was expressed to high levels. Among squamous cell carcinomas of the cervix uteri expression levels were lower and expression patterns were less intense, but still ranged between 50–60% (57%). A significant correlation between Mesothelin expression levels and tumor grade, metastatic behaviour, and lymph- or hemangiosis was not found. The novel anti-Mesothelin-drug conjugate (Anetumab Ravtansine) showed a substantial dose-dependent therapeutic efficiency in a xenotransplant model for cervical cancer in SCID mice (hela cell tumors). Applying the ADC at a dose of 10 mg/kg twice weekly induced complete tumor regression in 88% of animals within 6 weeks.

Conclusions

Mesothelin should be taken into account as a target in cervical cancer therapy and histological determination of Mesothelin expression should be considered in routine diagnostics of cervical carcinomas.

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Acknowledgements

This study was funded by the Bundesministerium für Bildung und Forschung (BMBF) 03V0347 and the Bayer AG. The authors would like to thank Natalie Kuzaj and Andrea Wilke for the excellent technical support.

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Authors and Affiliations

  1. Department of Pathology, Charité-Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany

    Korinna Jöhrens

  2. Department of Gynecology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Lea Lazzerini, Jana Barinoff, Jalid Sehouli & Guenter Cichon

Authors
  1. Korinna Jöhrens
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  2. Lea Lazzerini
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  3. Jana Barinoff
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  4. Jalid Sehouli
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  5. Guenter Cichon
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Contributions

KJ investigation and methodology; LL methodology; JB writing, review, and editing; JS supervision; GC conceptualization, writing, review, and editing.

Corresponding author

Correspondence to Guenter Cichon.

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Conflict of interest

Dr. Cichon received grant monies from Bayer AG. Prof. Sehouli receives funding for studies in ovarian cancer and serves on the Advisory Board as a consultant for Bayer. The other authors have no conflict of interest to declare.

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Jöhrens, K., Lazzerini, L., Barinoff, J. et al. Mesothelin as a target for cervical cancer therapy. Arch Gynecol Obstet 299, 211–216 (2019). https://doi.org/10.1007/s00404-018-4933-z

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  • DOI: https://doi.org/10.1007/s00404-018-4933-z

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