Control of mesothelin-expressing ovarian cancer using adoptive transfer of mesothelin peptide-specific CD8+ T cells.
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.
Hung
C-F
CF
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. chung2@jhmi.edu
Tsai
Y-C
YC
He
L
L
Wu
T-C
TC
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D007118:Immunoassay / Q000379:methods; D008156:Luciferases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D000090204:Mesothelin; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C000715528:Msln protein, mouse; D008156:Luciferases; D000090204:Mesothelin