Control of mesothelin-expressing ovarian cancer using adoptive transfer of mesothelin peptide-specific CD8+ T cells

Gene Ther. 2007 Jun;14(12):921-9. doi: 10.1038/sj.gt.3302913. Epub 2007 Mar 22.

Abstract

Cancer immunotherapy targeting mesothelin represents a potentially plausible approach for the control of ovarian cancer as most ovarian cancers express high levels of mesothelin. In the current study, we created a mesothelin-positive luciferase-expressing ovarian cancer model, MOSEC/luc. This luciferase-expressing tumor model allowed us to quantitate tumor distribution and tumor load in tumor-challenged mice using a non-invasive bioluminescence imaging system. In addition, we identified an H-2D(b)-restricted mesothelin peptide-specific cytotoxic T-lymphocyte (CTL) epitope (amino acid (aa) 406-414) that was endogenously processed and presented by MOSEC/luc tumor cells. We showed that adoptive transfer of mesothelin peptide (aa406-414)-specific CD8(+) T cells led to the control of MOSEC/luc tumor cells. The MOSEC/luc tumor model and the newly identified H-2D(b)-restricted murine mesothelin-specific CTL epitope (aa406-414) will be very useful for the development of immunotherapy for ovarian cancer as well as for the development of quantitative CD8(+) T cell-mediated immunological assays.

Publication types

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

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • CD8 Antigens / immunology*
  • Cancer Vaccines
  • Cell Line, Tumor
  • Cytokines / analysis
  • Cytokines / immunology
  • Epitopes / immunology
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins
  • Immunoassay / methods
  • Luciferases / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Neoplasm Transplantation
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / therapy*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • CD8 Antigens
  • Cancer Vaccines
  • Cytokines
  • Epitopes
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • Luciferases
  • mesothelin