Original Article

Gene Therapy (2007) 14, 921–929; doi:10.1038/sj.gt.3302913; published online 22 March 2007

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

C-F Hung1, Y-C Tsai1, L He1 and T-C Wu1,2,3,4

  1. 1Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
  2. 2Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
  3. 3Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
  4. 4Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Correspondence: Dr C-F Hung, Department of Pathology, The Johns Hopkins University School of Medicine, CRB II Room 307, 1550 Orleans Street, Baltimore, MD 21231, USA. E-mail: chung2@jhmi.edu

Received 28 July 2006; Revised 9 November 2006; Accepted 27 November 2006; Published online 22 March 2007.

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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-2Db-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-2Db-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.

Keywords:

immunotherapy, mesothelin, ovarian cancer, adoptive T cells

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