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...

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Bibliographic Details
Published in:	Cancer gene therapy Vol. 10; no. 9; pp. 678 - 688
Main Authors:	O, InSug, Blaszczyk-Thurin, Magdalena, Shen, Chunpang T, Ertl, Hildegund C J
Format:	Journal Article
Language:	English
Published:	England Nature Publishing Group 01-09-2003
Subjects:	Adaptive immunity Animals Antigens Antigens, Neoplasm Brain cancer Brain Neoplasms - immunology Brain Neoplasms - pathology Brain Neoplasms - prevention & control Care and treatment CD4 antigen CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell Line, Tumor Deoxyribonucleic acid DNA DNA vaccines Dopachrome isomerase Gene expression Genetic aspects Glioblastoma Glioblastoma - immunology Glioblastoma - pathology Glioblastoma - prevention & control Glioblastoma cells Glioblastoma multiforme Health aspects Humans Immunotherapy Interleukin 12 Intramolecular Oxidoreductases - genetics Intramolecular Oxidoreductases - immunology Intravenous administration Lung Neoplasms - immunology Lung Neoplasms - pathology Lung Neoplasms - prevention & control Lymphocytes T Melanin Melanoma Melanoma-associated antigen Melanoma-Specific Antigens Mice Mice, Inbred C57BL Mice, Knockout Neoplasm Proteins - genetics Neoplasm Proteins - immunology Neoplasm Proteins - metabolism Neoplasm Transplantation Physiological aspects Survival Rate Time Factors Vaccination Vaccine efficacy Vaccines Vaccines, DNA - genetics Vaccines, DNA - immunology United States
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0929-1903 1476-5500
DOI:	10.1038/sj.cgt.7700620