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Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma.

Abstract
Lentivectors are potential vaccine delivery vehicles because they can efficiently transduce a variety of non-dividing cells, including antigen-presenting cells, and do not cause expression of extra viral proteins. To improve safety while retaining efficiency, a dendritic cell (DC)-specific lentivector was constructed by pseudotyping the vector with an engineered viral glycoprotein derived from Sindbis virus. We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model. Footpad injection of the engineered lentivectors results in the best antigen-specific immune response as compared with subcutaneous and intraperitoneal injections. A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8(+) T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks. We found that these engineered lentivectors elicited relatively low levels of anti-vector neutralizing antibody responses. Importantly, direct injection of this engineered lentivector inhibited the growth of aggressive B16 murine melanoma. These data suggest that DC-specific lentivectors can be a novel and alternative vaccine carrier with the potential to deliver effective anti-tumor immunity for cancer immunotherapy.
AuthorsH G Yang, B L Hu, L Xiao, P Wang
JournalCancer gene therapy (Cancer Gene Ther) Vol. 18 Issue 5 Pg. 370-80 (May 2011) ISSN: 1476-5500 [Electronic] England
PMID21372855 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2011 Nature America, Inc.
Chemical References
  • Cancer Vaccines
  • Cytokines
  • DNA Primers
Topics
  • Animals
  • CD8-Positive T-Lymphocytes (immunology)
  • Cancer Vaccines (administration & dosage, immunology)
  • Cytokines (immunology)
  • DNA Primers (genetics)
  • Dendritic Cells (metabolism, virology)
  • Enzyme-Linked Immunospot Assay
  • Female
  • Flow Cytometry
  • Genetic Therapy (methods)
  • Genetic Vectors (administration & dosage, immunology)
  • Immunotherapy (methods)
  • Lentivirus
  • Melanoma (genetics, immunology, therapy)
  • Mice
  • Mice, Inbred C57BL
  • Neutralization Tests

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