Mesothelin, a novel immunotherapy target for triple negative breast cancer

Breast Cancer Res Treat. 2012 Jun;133(2):799-804. doi: 10.1007/s10549-012-2018-4. Epub 2012 Mar 15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Cohort Studies
  • Female
  • GPI-Linked Proteins / immunology*
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunotherapy*
  • Receptor, ErbB-2 / deficiency
  • Receptors, Estrogen / deficiency
  • Receptors, Progesterone / deficiency
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transduction, Genetic

Substances

  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2
  • mesothelin