A DNA vaccine expressing tyrosinase-related protein-2 induces T-cell-mediated protection against mouse glioblastoma.

Abstract

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.

• Authors: InSug O, Magdalena Blaszczyk-Thurin, Chunpang T Shen, Hildegund C J Ertl
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 10 Issue 9 Pg. 678-88 (Sep 2003) ISSN: 0929-1903 [Print] England
• PMID: 12944987 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Melanoma-Specific Antigens
• Neoplasm Proteins
• Vaccines, DNA
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Animals
• Antigens, Neoplasm
• Brain Neoplasms (immunology, pathology, prevention & control)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Line, Tumor
• Glioblastoma (immunology, pathology, prevention & control)
• Humans
• Intramolecular Oxidoreductases (genetics, immunology)
• Lung Neoplasms (immunology, pathology, prevention & control)
• Melanoma-Specific Antigens
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neoplasm Proteins (genetics, immunology, metabolism)
• Neoplasm Transplantation
• Survival Rate
• Time Factors
• Vaccination
• Vaccines, DNA (genetics, immunology)