A DNA vaccine expressing tyrosinase-related protein-2 induces T-cell-mediated protection against mouse glioblastoma.
A mouse glioblastoma cell line, termed GL261, was shown to express high levels of proteins involved in melanin biosynthesis such as the tyrosinase-related protein-2 (TRP-2), which is commonly overexpressed in melanoma cells. Mice injected with GL261 cells developed a CD8(+) T-cell response to TRP-2 and a DNA vaccine expressing human (h)TRP-2 induced CD8(+) T cells that recognized TRP-2 expressed by GL261 cells indicating that this melanoma-associated antigen may be suited for active immunotherapy of glioblastoma. Mice vaccinated with a DNA vaccine expressing TRP-2 were partially protected against subcutaneous, intravenous, or intracerebral challenge with the glioblastoma cells. Vaccine-induced protection against intracerebral challenge required both CD4(+) and CD8(+) T cells. Vaccine efficacy was enhanced upon addition of IL-12 as a genetic adjuvant. These results indicate that this well-defined melanoma-associated antigen can induce an adaptive immune response, which limits the intracerebral progression of a glioblastoma.
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InSug
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The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Blaszczyk-Thurin
Magdalena
M
Shen
Chunpang T
CT
Ertl
Hildegund C J
HC
D000818:Animals; D000951:Antigens, Neoplasm; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009368:Neoplasm Transplantation; D015996:Survival Rate; D013997:Time Factors; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D019444:Vaccines, DNA; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase