Efficient transduction of dendritic cells and induction of a T-cell response by third-generation lentivectors.

Abstract

In order to induce a therapeutic T lymphocyte response, recombinant viral vaccines are designed to target professional antigen-presenting cells (APC) such as dendritic cells (DC). A key requirement for their use in humans is safe and efficient gene delivery. The present study assesses third-generation lentivectors with respect to their ability to transduce human and mouse DC and to induce antigen-specific CD8+ T-cell responses. We demonstrate that third-generation lentivectors transduce DC with a superior efficiency compared to adenovectors. The transfer of DC transduced with a recombinant lentivector encoding an antigenic epitope resulted in a strong specific CD8+ T-cell response in mice. The occurrence of lower proportions of nonspecifically activated CD8+ cells suggests a lower antivector immunity of lentivector compared to adenovector. Thus, lentivectors, in addition to their promise for gene therapy of brain disorders might also be suitable for immunotherapy.

• Authors: Christoph Esslinger, Pedro Romero, H Robson MacDonald
• Journal: Human gene therapy (Hum Gene Ther) Vol. 13 Issue 9 Pg. 1091-100 (Jun 10 2002) ISSN: 1043-0342 [Print] United States
• PMID: 12067442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• Interferon-gamma

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Dendritic Cells (metabolism)
• Epitopes, T-Lymphocyte (genetics, immunology)
• Genetic Vectors (genetics, metabolism)
• HIV-1 (genetics)
• Humans
• Interferon-gamma (metabolism)
• Lentivirus (genetics, metabolism)
• Mice
• Mice, Transgenic
• Phenotype
• T-Lymphocytes (immunology)
• Transduction, Genetic