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PMID: 17377599 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Gene therapy ·Vol. 14 ·No. 12 ·2007-06-00 ·Pages 921-9

Hung CF, Tsai YC, He L, Wu TC

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.

MeSH Terms
Adoptive Transfer/methods Animals CD8 Antigens/immunology Cancer Vaccines Cell Line, Tumor Cytokines/analysis,immunology Epitopes/immunology Female Flow Cytometry GPI-Linked Proteins Immunoassay/methods Luciferases/metabolism Membrane Glycoproteins/genetics,immunology Mesothelin Mice Mice, Inbred C57BL Models, Animal Neoplasm Transplantation Ovarian Neoplasms/immunology,therapy Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Cytotoxic/immunology
Chemicals
CD8 Antigens Cancer Vaccines Cytokines Epitopes GPI-Linked Proteins Membrane Glycoproteins Msln protein, mouse Luciferases Mesothelin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hung C-F
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. chung2@jhmi.edu
Tsai Y-C
He L
Wu T-C
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Article Info
Journal
Gene therapy
Abbr.
Gene Ther
ISSN
0969-7128
DOI
10.1038/sj.gt.3302913
Email
chung2@jhmi.edu
Published
2007-06-00
Epub
2007-00-22
Pages
921-9
Language
English
Region
England
NLM ID
9421525
PMCID
PMC3183576
Subset
IM
Grants
NCI NIH HHS · U19 CA113341 · United States
NCI NIH HHS · 1U19 CA113341-01 · United States
External Links
PubMed source DOI: 10.1038/sj.gt.3302913 PMC Full Text View journal details
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