Abstract
DNA-based cancer vaccines have been used successfully in mice to induce cytotoxic T lymphocytes (CTLs) specific for prostate antigens. Translation of a prostate-specific antigen (PSA) DNA vaccine into a phase I clinical trial demonstrated that PSA-specific immune responses could be induced but at a significantly lower level compared with those in mice. To enhance the efficacy of DNA vaccination against prostate cancer, we have explored and optimized intradermal electroporation as an effective way of delivering a PSA DNA vaccine. The results demonstrated that intradermal DNA vaccination using low amounts of DNA, followed by two sets of electrical pulses of different length and voltage, effectively induced PSA-specific T cells. Here we describe in detail how to perform intradermal DNA electroporation to induce high gene expression in skin and, more important, how to induce and analyze PSA-specific T cell responses.
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References
1. Ferlay, J., Bray, F., Pisani, P., and Parkin, D.M. (2004) GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC CancerBase. IARC Press, Lyon.
2. Pavlenko, M., Roos, A.K., Leder, C., et al. (2004) Comparison of PSA-specific CD8+ CTL responses and antitumor immunity generated by plasmid DNA vaccines encoding PSA-HSP chimeric proteins. Cancer Immunol. Immunother. 53, 1085–1092.
3. Roos, A.K., Pavlenko, M., Charo, J., Egevad, L., and Pisa, P. (2005) Induction of PSA-specific CTLs and anti-tumor immunity by a genetic prostate cancer vaccine. Prostate. 62, 217–223.
4. Pavlenko, M., Roos, A.K., Lundqvist, A., et al. (2004) A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer. Br. J. Cancer. 91, 688–694.
5. Draghia-Akli, R., Khan, A.S., Pope, M.A., and Brown, P.A. (2005) Innovative electroporation for therapeutic and vaccination applications. Gene Ther. Mol. Biol. 9, 329–338.
6. Otten, G., Schaefer, M., Doe, B., et al. (2004) Enhancement of DNA vaccine potency in rhesus macaques by electroporation. Vaccine. 22, 2489–2493.
7. Babiuk, S., Baca-Estrada, M.E., Foldvari, M., et al. (2002) Electroporation improves the efficacy of DNA vaccines in large animals. Vaccine. 20, 3399–3408.
8. Prud'homme, G.J., Glinka, Y., Khan, A.S., and Draghia-Akli, R. (2006) Electroporation-enhanced nonviral gene transfer for the prevention or treatment of immunological, endocrine and neoplastic diseases. Curr. Gene Ther. 6, 243–273.
9. Corr, M., von Damm, A., Lee, D.J., and Tighe, H. (1999) In vivo priming by DNA injection occurs predominantly by antigen transfer. J. Immunol. 163, 4721–4727.
10. Cho, J.H., Youn, J.W., and Sung, Y.C. (2001) Cross-priming as a predominant mechanism for inducing CD8(+) T cell responses in gene gun DNA immunization. J. Immunol. 167, 5549–5557.
11. Peachman, K.K., Rao, M., and Alving, C.R. (2003) Immunization with DNA through the skin. Methods. 31, 232–242.
12. Roos, A.K., Moreno, S., Leder, C., Pavlenko, M., King, A., and Pisa, P. (2006) Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation. Mol. Ther. 13, 320–327.
13. Pavlenko, M., Leder, C., Roos, A.K., Levitsky, V., and Pisa, P. (2005) Identification of an immunodominant H-2D(b)-restricted CTL epitope of human PSA. Prostate. 64, 50–59.
14. Heller, R., Jaroszeski, M., Atkin, A., et al. (1996) In vivo gene electroinjection and expression in rat liver. FEBS Lett. 389, 225–228.
15. Heller, R., Jaroszeski, M.J., Reintgen, D.S., et al. (1998) Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin. Cancer. 83, 148–157.
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© 2008 Humana Press
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Roos, AK., King, A., Pisa, P. (2008). DNA Vaccination for Prostate Cancer. In: Li, S. (eds) Electroporation Protocols. Methods in Molecular Biology™, vol 423. Humana Press. https://doi.org/10.1007/978-1-59745-194-9_36
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DOI: https://doi.org/10.1007/978-1-59745-194-9_36
Publisher Name: Humana Press
Print ISBN: 978-1-58829-877-5
Online ISBN: 978-1-59745-194-9
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