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

Cancer Gene Therapy volume 18, pages 370–380 (2011)Cite this article

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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.

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Acknowledgements

We thank Steven Froelich and April Tai for critical reading of the manuscript. This work was supported by a National Institute of Health grant.

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  1. Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA

    H G Yang, B L Hu, L Xiao & P Wang

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  1. H G Yang
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Correspondence to P Wang.

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Yang, H., Hu, B., Xiao, L. et al. Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma. Cancer Gene Ther 18, 370–380 (2011). https://doi.org/10.1038/cgt.2011.13

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