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