Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation.
Recently it has become clear that more potent methods for DNA vaccine delivery need to be developed to enhance the efficacy of DNA vaccines. In vivo electroporation has emerged as a potent method for DNA vaccine delivery. In a mouse model, we evaluated the CD8(+) T lymphocyte response to a prostate cancer DNA vaccine encoding prostate-specific antigen (PSA) after intradermal electroporation. A significantly increased gene expression (100- to 1000-fold) and higher levels of PSA-specific T cells, compared to DNA delivery without electroporation, was demonstrated. Interestingly, investigation of a panel of different electroporation conditions showed that only some conditions that induce high levels of gene expression additionally induced cellular immunity. This suggests that electroporation parameters should be carefully optimized, not only to enhance transfection efficiency, but also to enhance the immune response to the vaccine. This study demonstrates the applicability of intradermal electroporation as a delivery method for genetic cancer vaccines and other DNA vaccines relying on antigen-specific T cell induction.
Roos
Anna-Karin
AK
Cancer Center Karolinska R8:01, Immune and Gene Therapy Laboratory, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden. anna-karin.roos@cck.ki.se
Moreno
Sonia
S
Leder
Christoph
C
Pavlenko
Maxim
M
King
Alan
A
Pisa
Pavel
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018274:Electroporation / Q000295:instrumentation; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics; D007271:Injections, Intradermal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017430:Prostate-Specific Antigen / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D019076:Transgenes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D019444:Vaccines, DNA; D017430:Prostate-Specific Antigen