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Breast Cancer Research and Treatment

, Volume 133, Issue 2, pp 799–804 | Cite as

Mesothelin, a novel immunotherapy target for triple negative breast cancer

  • Julia TchouEmail author
  • Liang-Chuan Wang
  • Ben Selven
  • Hongtao Zhang
  • Jose Conejo-Garcia
  • Hossein Borghaei
  • Michael Kalos
  • Robert H. Vondeheide
  • Steven M. Albelda
  • Carl H. June
  • Paul J. Zhang
Brief Report

Abstract

Mesothelin is a cell-surface glycoprotein present on mesothelial cells and elicits T cell responses in a variety of cancers including pancreatic, biliary and ovarian cancer. Breast cancer is not known to express mesothelin. We postulated that mesothelin may be a unique tumor-associated antigen in triple negative breast cancer (TNBC), a less common breast cancer subtype which may have been under-represented in prior studies that characterized mesothelin expression. Therefore, we screened 99 primary breast cancer samples by immunohistochemistry analysis using formalin-fixed paraffin-embedded archival tumor tissues and confirmed that mesothelin was overexpressed in the majority of TNBC (67 %) but only rarely in <5 % ER(+) or Her2-neu(+) breast cancer, respectively. To determine whether mesothelin may be exploited as a novel immunotherapy target in breast cancer, an in vitro cell killing assay was performed to compare the ability of genetically modified T cells expressing a chimeric antibody receptor (CAR) specific for mesothelin (mesoCAR T cells) or non-transduced T cells to kill mesothelin-expressing primary breast cancer cells. A significantly higher anti-tumor cytotoxicity by mesoCAR T cells was observed (31.7 vs. 8.7 %, p < 0.001). Our results suggest that mesothelin has promise as a novel immunotherapy target for TNBC for which effective targeted therapy is lacking to date.

Keywords

Mesothelin Breast cancer subtypes Triple negative breast cancer Chimeric antigen receptor Immunotherapy 

Notes

Acknowledgments

This study was, in part, funded by a pilot grant from NCI CCSG 2-P30-CA-016520-35 and the Abramson Cancer Center Richardson Breast Cancer Research Fund to JT; and by Pennsylvania Department of Health grant #0972501 to RHV and CHJ.

Conflict of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Julia Tchou
    • 1
    • 2
    • 8
    Email author
  • Liang-Chuan Wang
    • 3
  • Ben Selven
    • 1
  • Hongtao Zhang
    • 4
  • Jose Conejo-Garcia
    • 5
  • Hossein Borghaei
    • 6
  • Michael Kalos
    • 2
    • 4
    • 7
  • Robert H. Vondeheide
    • 2
    • 7
  • Steven M. Albelda
    • 3
  • Carl H. June
    • 2
    • 4
    • 7
  • Paul J. Zhang
    • 4
  1. 1.Division of Endocrine and Oncologic Surgery, Department of Surgery, and the Rena Rowan Breast Center, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Abramson Cancer Center, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Thoracic Oncology Research Laboratory, Pulmonary Division, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Pathology and Lab Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Tumor Microenvironment and Metastasis ProgramThe Wistar InstitutePhiladelphiaUSA
  6. 6.Fox Chase Cancer CenterPhiladelphiaUSA
  7. 7.Abramson Family Cancer Research Institute, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  8. 8.Perelman Center for Advanced MedicinePhiladelphiaUSA

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