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

• DOI: 10.1038/cgt.2011.13
• Publication Date: 2011-03-04T11:59:45Z
• Authors: H G Yang; B L Hu; L Xiao; P Wang
• Keywords: Enzyme-Linked Immunospot Assay; 0303 health sciences; Genetic Vectors; Lentivirus; Dendritic Cells; Genetic Therapy; CD8-Positive T-Lymphocytes; Flow Cytometry; Cancer Vaccines; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Neutralization Tests; Animals; Cytokines; Female; Immunotherapy; Melanoma; DNA Primers

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.