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Tapping the Potential of DNA Delivery with Electroporation for Cancer Immunotherapy

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Cancer Vaccines

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 405))

Abstract

Cancer is a worldwide leading cause of death, and current conventional therapies are limited. The search for alternative preventive or therapeutic solutions is critical if we are going to improve outcomes for patients. The potential for DNA vaccines in the treatment and prevention of cancer has gained great momentum since initial findings almost 2 decades ago that revealed that genetically engineered DNA can elicit an immune response. The combination of adjuvants and an effective delivery method such as electroporation is overcoming past setbacks for naked plasmid DNA (pDNA) as a potential preventive or therapeutic approach to cancer in large animals and humans. In this chapter, we aim to focus on the novel advances in recent years for DNA cancer vaccines, current preclinical data, and the importance of adjuvants and electroporation with emphasis on prostate, melanoma, and cervical cancer.

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References

  • Abdulla A, Kapoor A (2011) Emerging novel therapies in the treatment of castrate-resistant prostate cancer. Can Urol Assoc J (Journal de l’Association des urologues du Canada) 5(2):120–133. doi:10.5489/cuaj.10160

    Article  Google Scholar 

  • Adamo V, Noto L, Franchina T, Chiofalo G, Picciotto M, Toscano G, Caristi N (2012) Emerging targeted therapies for castration-resistant prostate cancer. Front Endocrinol 3:73. doi:10.3389/fendo.2012.00073

    Article  CAS  Google Scholar 

  • Agarwal N, Di Lorenzo G, Sonpavde G, Bellmunt J (2014) New agents for prostate cancer. Ann Oncol Official J Eur Soc Med Oncol/ESMO 25(9):1700–1709. doi:10.1093/annonc/mdu038

    Article  CAS  Google Scholar 

  • Aggarwal P (2014) Cervical cancer: can it be prevented? World J Clin Oncol 5 (4):775–780. doi:10.5306/wjco.v5.i4.775

  • Ahmad S, Casey G, Sweeney P, Tangney M, O’Sullivan GC (2009) Prostate stem cell antigen DNA vaccination breaks tolerance to self-antigen and inhibits prostate cancer growth. Mol Ther: J Am Soc Gene Ther 17(6):1101–1108. doi:10.1038/mt.2009.66

    Article  CAS  Google Scholar 

  • Ahmad S, Casey G, Sweeney P, Tangney M, O’Sullivan GC (2010) Optimised electroporation mediated DNA vaccination for treatment of prostate cancer. Genet Vaccines Ther 8(1):1. doi:10.1186/1479-0556-8-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Bagarazzi ML, Yan J, Morrow MP, Shen X, Parker RL, Lee JC, Giffear M, Pankhong P, Khan AS, Broderick KE, Knott C, Lin F, Boyer JD, Draghia-Akli R, White CJ, Kim JJ, Weiner DB, Sardesai NY (2012) Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med 4(155):155ra138

    Google Scholar 

  • Best SR, Peng S, Juang CM, Hung CF, Hannaman D, Saunders JR, Wu TC, Pai SI (2009) Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery. Vaccine 27(40):5450–5459. doi:10.1016/j.vaccine.2009.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bodles-Brakhop AM, Draghia-Akli R (2008) DNA vaccination and gene therapy: optimization and delivery for cancer therapy. Expert Rev Vaccines 7(7):1085–1101

    Article  CAS  PubMed  Google Scholar 

  • Bodles-Brakhop AM, Heller R, Draghia-Akli R (2009) Electroporation for the delivery of DNA-based vaccines and immunotherapeutics: current clinical developments. Mol Ther 17(4):585–592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broderick KE, Chan A, Lin F, Shen X, Kichaev G, Khan AS, Aubin J, Zimmermann TS, Sardesai NY (2012) Optimized in vivo transfer of small interfering RNA targeting dermal tissue using in vivo surface electroporation. Mol Ther Nucleic Acids 1:e11. doi:10.1038/mtna.2012.1

    Article  PubMed  PubMed Central  Google Scholar 

  • Broderick KE, Khan AS, Sardesai NY (2014) DNA vaccination in skin enhanced by electroporation. Methods Mol Biol (Clifton, NJ) 1143:123–130. doi:10.1007/978-1-4939-0410-5_8

  • Buchan S, Gronevik E, Mathiesen I, King CA, Stevenson FK, Rice J (2005) Electroporation as a “prime/boost” strategy for naked DNA vaccination against a tumor antigen. J Immunol 174(10):6292–6298

    Article  CAS  PubMed  Google Scholar 

  • Calvet CY, Thalmensi J, Liard C, Pliquet E, Bestetti T, Huet T, Langlade-Demoyen P, Mir LM (2014) Optimization of a gene electrotransfer procedure for efficient intradermal immunization with an hTERT-based DNA vaccine in mice. Mol Ther Methods Clin Dev 1. doi:10.1038/mtm.2014.45

  • Chan RC, Gutierrez B, Ichim TE, Lin F (2009) Enhancement of DNA cancer vaccine efficacy by combination with anti-angiogenesis in regression of established subcutaneous B16 melanoma. Oncol Rep 22(5):1197–1203

    CAS  PubMed  Google Scholar 

  • Curcio C, Khan AS, Amici A, Spadaro M, Quaglino E, Cavallo F, Forni G, Draghia-Akli R (2008) DNA immunization using constant-current electroporation affords long-term protection from autochthonous mammary carcinomas in cancer-prone transgenic mice. Cancer Gene Ther 15(2):108–114

    Article  CAS  PubMed  Google Scholar 

  • Denies S, Cicchelero L, Van Audenhove I, Sanders NN (2014) Combination of interleukin-12 gene therapy, metronomic cyclophosphamide and DNA cancer vaccination directs all arms of the immune system towards tumor eradication. J Control Release 187:175–182. doi:10.1016/j.jconrel.2014.05.045

    Article  CAS  PubMed  Google Scholar 

  • DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS, Jemal A (2014) Cancer treatment and survivorship statistics, 2014. CA: A Cancer J Clin 64(4):252–271. doi:10.3322/caac.21235

    Google Scholar 

  • Ferraro B, Cisper NJ, Talbott KT, Philipson-Weiner L, Lucke CE, Khan AS, Sardesai NY, Weiner DB (2011) Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses. Hum Vaccine 7:120–127

    Article  CAS  Google Scholar 

  • Ferraro B, Talbott KT, Balakrishnan A, Cisper N, Morrow MP, Hutnick NA, Myles DJ, Shedlock DJ, Obeng-Adjei N, Yan J, Kayatani AK, Richie N, Cabrera W, Shiver R, Khan AS, Brown AS, Yang M, Wille-Reece U, Birkett AJ, Sardesai NY, Weiner DB (2013) Inducing humoral and cellular responses to multiple sporozoite and liver-stage malaria antigens using exogenous plasmid DNA. Infect Immun 81(10):3709–3720. doi:10.1128/iai.00180-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flingai S, Czerwonko M, Goodman J, Kudchodkar SB, Muthumani K, Weiner DB (2013) Synthetic DNA vaccines: improved vaccine potency by electroporation and co-delivered genetic adjuvants. Front Immunol 4:354. doi:10.3389/fimmu.2013.00354

    Article  PubMed  PubMed Central  Google Scholar 

  • Gabai V, Venanzi FM, Bagashova E, Rud O, Mariotti F, Vullo C, Catone G, Sherman MY, Concetti A, Chursov A, Latanova A, Shcherbinina V, Shifrin V, Shneider A (2014) Pilot study of p62 DNA vaccine in dogs with mammary tumors. Oncotarget 5(24):12803–12810

    Article  PubMed  PubMed Central  Google Scholar 

  • Gan L, Jia R, Zhou L, Guo J, Fan M (2014) Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine. PLoS One 9(9):e108892. doi:10.1371/journal.pone.0108892

    Article  PubMed  PubMed Central  Google Scholar 

  • Gavazza A, Lubas G, Fridman A, Peruzzi D, Impellizeri JA, Luberto L, Marra E, Roscilli G, Ciliberto G, Aurisicchio L (2013) Safety and efficacy of a genetic vaccine targeting telomerase plus chemotherapy for the therapy of canine B-cell lymphoma. Hum Gene Ther 24(8):728–738. doi:10.1089/hum.2013.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han KT, Sin JI (2013) DNA vaccines targeting human papillomavirus-associated diseases: progresses in animal and clinical studies. Clin Exp Vaccine Res 2(2):106–114. doi:10.7774/cevr.2013.2.2.106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heller L, Pottinger C, Jaroszeski MJ, Gilbert R, Heller R (2000) In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunity. Melanoma Res 10(6):577–583

    Article  CAS  PubMed  Google Scholar 

  • Heller LC, Heller R (2010) Electroporation gene therapy preclinical and clinical trials for melanoma. Curr Gene Ther 10(4):312–317

    Article  CAS  PubMed  Google Scholar 

  • Hirao L, Wu L, Khan AS, Hokey D, Yan J, Dai A, Betts M, Draghia-Akli R, Weiner DB (2008) Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques. Vaccine 26(25):3112–3120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirao LA, Draghia-Akli R, Prigge JT, Yang M, Satishchandran A, Wu L, Hammarlund E, Khan AS, Babas T, Rhodes L, Silvera P, Slifka M, Sardesai NY, Weiner DB (2011) Multivalent smallpox DNA vaccine delivered by intradermal electroporation drives protective immunity in nonhuman primates against lethal monkeypox challenge. J Infect Dis 203(1):95–102. doi:10.1093/infdis/jiq017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirao LA, Wu L, Satishchandran A, Khan AS, Draghia-Akli R, Finnefrock AC, Bett AJ, Betts MR, Casimiro DR, Sardesai NY, Kim JJ, Shiver JW, Weiner DB (2010) Comparative analysis of immune responses induced by vaccination with SIV antigens by recombinant Ad5 vector or plasmid DNA in rhesus macaques. Mol Ther J Am Soc Gene Ther 18(8):1568–1576. doi:10.1038/mt.2010.112

    Article  CAS  Google Scholar 

  • Hutnick NA, Myles DJ, Ferraro B, Lucke C, Lin F, Yan J, Broderick KE, Khan AS, Sardesai NY, Weiner DB (2012) Intradermal DNA vaccination enhanced by low-current electroporation improves antigen expression and induces robust cellular and humoral immune responses. Hum Gene Ther 23(9):943–950. doi:10.1089/hum.2012.055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobs JJ, Snackey C, Geldof AA, Characiejus D, Van Moorselaar RJ, Den Otter W (2014) Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus prostate cancer. Anticancer Res 34(6):2689–2700

    CAS  PubMed  Google Scholar 

  • Jalah R, Patel V, Kulkarni V, Rosati M, Alicea C, Ganneru B, von Gegerfelt A, Huang W, Guan Y, Broderick KE, Sardesai NY, LaBranche C, Montefiori DC, Pavlakis GN, Felber BK (2012) IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques. Hum Vaccines Immunotherapeutics 8(11):1620–1629. doi:10.4161/hv.21407

    Article  CAS  Google Scholar 

  • Jalah R, Rosati M, Ganneru B, Pilkington GR, Valentin A, Kulkarni V, Bergamaschi C, Chowdhury B, Zhang GM, Beach RK, Alicea C, Broderick KE, Sardesai NY, Pavlakis GN, Felber BK (2013) The p40 subunit of interleukin (IL)-12 promotes stabilization and export of the p35 subunit: implications for improved IL-12 cytokine production. J Biol Chem 288(9):6763–6776. doi:10.1074/jbc.M112.436675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalams SA, Parker SD, Elizaga M, Metch B, Edupuganti S, Hural J, De Rosa S, Carter DK, Rybczyk K, Frank I, Fuchs J, Koblin B, Kim DH, Joseph P, Keefer MC, Baden LR, Eldridge J, Boyer J, Sherwat A, Cardinali M, Allen M, Pensiero M, Butler C, Khan AS, Yan J, Sardesai NY, Kublin JG, Weiner DB (2013) Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery. J Infect Dis 208(5):818–829. doi:10.1093/infdis/jit236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalat M, Kupcu Z, Schuller S, Zalusky D, Zehetner M, Paster W, Schweighoffer T (2002) In vivo plasmid electroporation induces tumor antigen-specific CD8+ T-cell responses and delays tumor growth in a syngeneic mouse melanoma model. Cancer Res 62(19):5489–5494

    CAS  PubMed  Google Scholar 

  • Khan AS, Broderick KE, Sardesai NY (2014) Clinical development of intramuscular electroporation: providing a “boost” for DNA vaccines. Methods in molecular biology (Clifton, NJ) 1121:279-289. doi:10.1007/978-1-4614-9632-8_25

  • Kim JJ, Trivedi NN, Wilson DM, Mahalingam S, Morrison L, Tsai A, Chattergoon MA, Dang K, Patel M, Ahn L, Boyer JD, Chalian AA, Schoemaker H, Kieber-Emmons T, Agadjanyan MA, Weiner DB (1998) Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine. Oncogene 17(24):3125–3135. doi:10.1038/sj.onc.1201736

    Article  CAS  PubMed  Google Scholar 

  • Kim JJ, Yang JS, Dang K, Manson KH, Weiner DB (2001a) Engineering enhancement of immune responses to DNA-based vaccines in a prostate cancer model in rhesus macaques through the use of cytokine gene adjuvants. Clin Cancer Res 7(3 Suppl):882s–889s

    CAS  PubMed  Google Scholar 

  • Kim JJ, Yang JS, Nottingham LK, Tang W, Dang K, Manson KH, Wyand MS, Wilson DM, Weiner DB (2001b) Induction of immune responses and safety profiles in rhesus macaques immunized with a DNA vaccine expressing human prostate specific antigen. Oncogene 20(33):4497–4506. doi:10.1038/sj.onc.1204542

    Article  CAS  PubMed  Google Scholar 

  • Kraynyak KA, Kutzler MA, Cisper NJ, Khan AS, Draghia-Akli R, Sardesal NY, Lewis MG, Yan J, Weiner DB (2010) Systemic immunization with CCL27/CTACK modulates immune responses at mucosal sites in mice and macaques. Vaccine 28(8):1942–1951. doi:10.1016/j.vaccine.2009.10.095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kutzler MA, Kraynyak KA, Nagle SJ, Parkinson RM, Zharikova D, Chattergoon M, Maguire H, Muthumani K, Ugen K, Weiner DB (2010) Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo. Gene Ther 17(1):72–82. doi:10.1038/gt.2009.112

    Article  CAS  PubMed  Google Scholar 

  • Kutzler MA, Weiner DB (2008) DNA vaccines: ready for prime time? Nat Rev Genet 9(10):776–788

    Google Scholar 

  • Laddy DJ, Yan J, Corbitt N, Kobasa D, Kobinger GP, Weiner DB (2007) Immunogenicity of novel consensus-based DNA vaccines against avian influenza. Vaccine 25(16):2984–2989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laddy DJ, Yan J, Khan AS, Anderson H, Cohn A, Greenhouse J, Lewis M, Manischewitz J, King LR, Golding H, Draghia-Akli R, Weiner DB (2009) Electroporation of synthetic DNA antigens offers protection in non-human primates challenged with highly pathogenic avian influenza. J Virol 83(9):4624–4630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laddy DJ, Yan J, Kutzler M, Kobasa D, Kobinger GP, Khan AS, Draghia-Akli R, Greenhouse J, Sardesai NY, Weiner DB (2008) Induction of heterosubtypic protection against pathogenic human and avian influenza viruses by synthetic consensus DNA antigens. Vaccine 3(6):e2517. doi:10.1371/journal.pone.0002517

    Google Scholar 

  • Lang KA, Yan J, Draghia-Akli R, Khan A, Weiner DB (2008) Strong HCV NS3- and NS4A-specific cellular immune responses induced in mice and Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine. Vaccine 26(49):6225–6231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Latimer B, Toporovski R, Yan J, Pankhong P, Morrow MP, Khan AS, Sardesai NY, Welles SL, Jacobson JM, Weiner DB, Kutzler MA (2014) Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine. Hum Vaccines Immunotherapeutics 10(8):2357–2365. doi:10.4161/hv.29590

    Article  CAS  Google Scholar 

  • Lin F, Shen X, Kichaev G, Mendoza JM, Yang M, Armendi P, Yan J, Kobinger GP, Bello A, Khan AS, Broderick KE, Sardesai NY (2012) Optimization of electroporation-enhanced intradermal delivery of DNA vaccine using a minimally invasive surface device. Hum Gene Ther Methods 23(3):157–168. doi:10.1089/hgtb.2011.209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin F, Shen X, McCoy JR, Mendoza JM, Yan J, Kemmerrer SV, Khan AS, Weiner DB, Broderick KE, Sardesai NY (2011) A novel prototype device for electroporation-enhanced DNA vaccine delivery simultaneously to both skin and muscle. Vaccine 29(39):6771–6780. doi:10.1016/j.vaccine.2010.12.057

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Geng S, Feng C, Xie X, Wu B, Chen X, Zou Q, Wang S, Cui J, Xing R, Li W, Lu Y, Wang B (2013) A DNA vaccine targeting p42.3 induces protective antitumor immunity via eliciting cytotoxic CD8+T lymphocytes in a murine melanoma model. Hum Vaccines Immunotherapeutics 9(10):2196–2202. doi:10.4161/hv.25013

  • Lladser A, Ljungberg K, Tufvesson H, Tazzari M, Roos AK, Quest AF, Kiessling R (2010) Intradermal DNA electroporation induces survivin-specific CTLs, suppresses angiogenesis and confers protection against mouse melanoma. Cancer Immunol Immunother CII 59(1):81–92. doi:10.1007/s00262-009-0725-4

    Article  CAS  PubMed  Google Scholar 

  • Lollini PL, Cavallo F, De Giovanni C, Nanni P (2013) Preclinical vaccines against mammary carcinoma. Expert Rev Vaccines 12(12):1449–1463. doi:10.1586/14760584.2013.845530

    Article  CAS  PubMed  Google Scholar 

  • Low L, Mander A, McCann K, Dearnaley D, Tjelle T, Mathiesen I, Stevenson F, Ottensmeier CH (2009) DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer. Hum Gene Ther 20(11):1269–1278

    Article  CAS  PubMed  Google Scholar 

  • Mao L, Sun W, Li W, Cui J, Zhang J, Xing R, Lu Y (2014) Cell cycle-dependent expression of p42.3 promotes mitotic progression in malignant transformed cells. Mol Carcinogenesis 53(5):337–348. doi:10.1002/mc.21982

    Article  CAS  Google Scholar 

  • Marur S, D’Souza G, Westra WH, Forastiere AA (2010) HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 11(8):781–789. doi:10.1016/s1470-2045(10)70017-6

    Article  PubMed  PubMed Central  Google Scholar 

  • McCray AN, Ugen KE, Heller R (2007) Enhancement of anti-melanoma activity of a plasmid expressing HIV-1 Vpr delivered through in vivo electroporation. Cancer Biol Ther 6(8):1269–1275

    Article  CAS  PubMed  Google Scholar 

  • McCray AN, Ugen KE, Muthumani K, Kim JJ, Weiner DB, Heller R (2006) Complete regression of established subcutaneous B16 murine melanoma tumors after delivery of an HIV-1 Vpr-expressing plasmid by in vivo electroporation. Mol Ther 14(5):647–655

    Article  CAS  PubMed  Google Scholar 

  • Morrow MP, Yan J, Pankhong P, Ferraro B, Lewis MG, Khan AS, Sardesai NY, Weiner DB (2010) Unique Th1/Th2 phenotypes induced during priming and memory phases by use of interleukin-12 (IL-12) or IL-28B vaccine adjuvants in rhesus macaques. Clin Vaccine Immunol CVI 17(10):1493–1499. doi:10.1128/cvi.00181-10

    Article  CAS  PubMed  Google Scholar 

  • Morrow MP, Yan J, Sardesai NY (2013) Human papillomavirus therapeutic vaccines: targeting viral antigens as immunotherapy for precancerous disease and cancer. Expert Rev Vaccines 12(3):271–283. doi:10.1586/erv.13.23

    Article  CAS  PubMed  Google Scholar 

  • Muthumani K, Lambert VM, Kawalekar O, Heller R, Kim JJ, Weiner DB, Ugen KE (2010) Anti-cancer activity of the HIV accessory molecule viral protein R (Vpr): Delivery as a DNA expression plasmid or biologically active peptides. Vaccine 28(8):2005–2010. doi:10.1016/j.vaccine.2009.10.060

    Article  CAS  PubMed  Google Scholar 

  • Muthumani K, Lambert VM, Shanmugam M, Thieu KP, Choo AY, Chung JC, Satishchandran A, Kim JJ, Weiner DB, Ugen KE (2009) Anti-tumor activity mediated by protein and peptide transduction of HIV viral protein R (Vpr). Cancer Biol Ther 8(2):180–187

    Article  CAS  PubMed  Google Scholar 

  • Muthumani K, Wise MC, Broderick KE, Hutnick N, Goodman J, Flingai S, Yan J, Bian CB, Mendoza J, Tingey C, Wilson C, Wojtak K, Sardesai NY, Weiner DB (2013) HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo. PLoS One 8(12):e84234. doi:10.1371/journal.pone.0084234

    Article  PubMed  PubMed Central  Google Scholar 

  • Norell H, Poschke I, Charo J, Wei WZ, Erskine C, Piechocki MP, Knutson KL, Bergh J, Lidbrink E, Kiessling R (2010) Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial. J Transl Med 8:53. doi:10.1186/1479-5876-8-53

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohlschlager P, Quetting M, Alvarez G, Durst M, Gissmann L, Kaufmann AM (2009) Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants. Int J Cancer 125(1):189–198

    Article  PubMed  Google Scholar 

  • Ohlschlager P, Spies E, Alvarez G, Quetting M, Groettrup M (2011) The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA. Int J Cancer J Int du Cancer 128(2):473–481. doi:10.1002/ijc.25344

    Article  Google Scholar 

  • Peruzzi D, Gavazza A, Mesiti G, Lubas G, Scarselli E, Conforti A, Bendtsen C, Ciliberto G, La Monica N, Aurisicchio L (2010) A vaccine targeting telomerase enhances survival of dogs affected by B-cell lymphoma. Mol Ther J Am Soc Gene Ther 18(8):1559–1567. doi:10.1038/mt.2010.104

    Article  CAS  Google Scholar 

  • Quaglino E, Iezzi M, Mastini C, Amici A, Pericle F, Di CE, Pupa SM, De GC, Spadaro M, Curcio C, Lollini PL, Musiani P, Forni G, Cavallo F (2004) Electroporated DNA vaccine clears away multifocal mammary carcinomas in her-2/neu transgenic mice. Cancer Res 64(8):2858–2864

    Article  CAS  PubMed  Google Scholar 

  • Radkevich-Brown O, Piechocki MP, Back JB, Weise AM, Pilon-Thomas S, Wei WZ (2010) Intratumoral DNA electroporation induces anti-tumor immunity and tumor regression. Cancer Immunol Immunother CII 59(3):409–417. doi:10.1007/s00262-009-0760-1

    Article  CAS  PubMed  Google Scholar 

  • Reiter RE, Gu Z, Watabe T, Thomas G, Szigeti K, Davis E, Wahl M, Nisitani S, Yamashiro J, Le Beau MM, Loda M, Witte ON (1998) Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci USA 95(4):1735–1740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riccardo F, Iussich S, Maniscalco L, Lorda Mayayo S, La Rosa G, Arigoni M, De Maria R, Gattino F, Lanzardo S, Lardone E, Martano M, Morello E, Prestigio S, Fiore A, Quaglino E, Zabarino S, Ferrone S, Buracco P, Cavallo F (2014) CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA. Clin Cancer Res Official J Am Assoc Cancer Res 20(14):3753–3762. doi:10.1158/1078-0432.ccr-13-3042

    Article  CAS  Google Scholar 

  • Roos AK, Eriksson F, Walters DC, Pisa P, King AD (2009) Optimization of skin electroporation in mice to increase tolerability of DNA vaccine delivery to patients. Mol Ther 17(9):1637–1642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roos AK, King A, Pisa P (2008) DNA vaccination for prostate cancer. In: Li S (ed) Methods in molecular biology. Electroporation protocols. Preclinical and clinical gene medicine, vol 423. Humana Press, Totowa, New Jersey, 07512, pp 463–472

    Google Scholar 

  • Roos AK, Moreno S, Leder C, Pavlenko M, King A, Pisa P (2006) Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation. Mol Ther 13(2):320–327

    Article  CAS  PubMed  Google Scholar 

  • Sajadian A, Tabarraei A, Soleimanjahi H, Fotouhi F, Gorji A, Ghaemi A (2014) Comparing the effect of Toll-like receptor agonist adjuvants on the efficiency of a DNA vaccine. Arch Virol 159(8):1951–1960. doi:10.1007/s00705-014-2024-4

    Article  CAS  PubMed  Google Scholar 

  • Saranga-Perry V, Ambe C, Zager JS, Kudchadkar RR (2014) Recent developments in the medical and surgical treatment of melanoma. CA Cancer J Clin 64(3):171–185. doi:10.3322/caac.21224

    Article  PubMed  Google Scholar 

  • Sardesai NY, Weiner DB (2011) Electroporation delivery of DNA vaccines: prospects for success. Curr Opin Immunol 23(3):421–429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seo SH, Jin HT, Park SH, Youn JI, Sung YC (2009) Optimal induction of HPV DNA vaccine-induced CD8+ T cell responses and therapeutic antitumor effect by antigen engineering and electroporation. Vaccine 27(42):5906–5912. doi:10.1016/j.vaccine.2009.07.033

    Article  CAS  PubMed  Google Scholar 

  • Shedlock DJ, Aviles J, Talbott KT, Wong G, Wu SJ, Villarreal DO, Myles DJ, Croyle MA, Yan J, Kobinger GP, Weiner DB (2013) Induction of broad cytotoxic T cells by protective DNA vaccination against Marburg and Ebola. Mol Ther J Am Soc Gene Ther 21(7):1432–1444. doi:10.1038/mt.2013.61

    Article  CAS  Google Scholar 

  • Shin TH, Pankhong P, Yan J, Khan AS, Sardesai NY, Weiner DB (2012) Induction of robust cellular immunity against HPV6 and HPV11 in mice by DNA vaccine encoding for E6/E7 antigen. Hum Vaccines Immunotherapeutics 8(4):470–478. doi:10.4161/hv.19180

    Article  CAS  Google Scholar 

  • Smorlesi A, Papalini F, Amici A, Orlando F, Pierpaoli S, Mancini C, Provinciali M (2006) Evaluation of different plasmid DNA delivery systems for immunization against HER2/neu in a transgenic murine model of mammary carcinoma. Vaccine 24(11):1766–1775

    Article  CAS  PubMed  Google Scholar 

  • Spies E, Reichardt W, Alvarez G, Groettrup M, Ohlschlager P (2012) An artificial PAP gene breaks self-tolerance and promotes tumor regression in the TRAMP model for prostate carcinoma. Mol Ther J Am Soc Gene Ther 20(3):555–564. doi:10.1038/mt.2011.241

    Article  CAS  Google Scholar 

  • Takeshita F, Tanaka T, Matsuda T, Tozuka M, Kobiyama K, Saha S, Matsui K, Ishii KJ, Coban C, Akira S, Ishii N, Suzuki K, Klinman DM, Okuda K, Sasaki S (2006) Toll-like receptor adaptor molecules enhance DNA-raised adaptive immune responses against influenza and tumors through activation of innate immunity. J Virol 80(13):6218–6224. doi:10.1128/jvi.00121-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venanzi F, Shifrin V, Sherman M, Gabai V, Kiselev O, Komissarov A, Grudinin M, Shartukova M, Romanovskaya-Romanko EA, Kudryavets Y, Bezdenezhnykh N, Lykhova O, Semesyuk N, Concetti A, Tsyb A, Filimonova M, Makarchuk V, Yakubovsky R, Chursov A, Shcherbinina V, Shneider A (2013) Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding vector. Oncotarget 4(10):1829–1835

    Article  PubMed  PubMed Central  Google Scholar 

  • Villarreal DO, Talbott KT, Choo DK, Shedlock DJ, Weiner DB (2013) Synthetic DNA vaccine strategies against persistent viral infections. Expert Rev Vaccines 12(5):537–554. doi:10.1586/erv.13.33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Villarreal DO, Wise MC, Walters JN, Reuschel EL, Choi MJ, Obeng-Adjei N, Yan J, Morrow MP, Weiner DB (2014) Alarmin IL-33 acts as an immunoadjuvant to enhance antigen-specific tumor immunity. Cancer Res 74(6):1789–1800. doi:10.1158/0008-5472.can-13-2729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247(4949 Pt 1):1465–1468

    Article  CAS  PubMed  Google Scholar 

  • Yan J, Harris K, Khan AS, Draghia-Akli R, Sewell DA, Weiner DB (2008) Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques. Vaccine 26(40):5210–5215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan J, Pankhong P, Shin TH, Obeng-Adjei N, Morrow MP, Walters JN, Khan AS, Sardesai NY, Weiner DB (2013) Highly optimized DNA vaccine targeting human telomerase reverse transcriptase stimulates potent antitumor immunity. Cancer Immunol Res 1(3):179–189. doi:10.1158/2326-6066.cir-13-0001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan J, Tingey C, Lyde R, Gorham TC, Choo DK, Muthumani A, Myles D, Weiner LP, Kraynyak KA, Reuschel EL, Finkel TH, Kim JJ, Sardesai NY, Ugen KE, Muthumani K, Weiner DB (2014a) Novel and enhanced anti-melanoma DNA vaccine targeting the tyrosinase protein inhibits myeloid-derived suppressor cells and tumor growth in a syngeneic prophylactic and therapeutic murine model. Cancer Gene Ther. doi:10.1038/cgt.2014.56

    Google Scholar 

  • Yan J, Villarreal DO, Racine T, Chu JS, Walters JN, Morrow MP, Khan AS, Sardesai NY, Kim JJ, Kobinger GP, Weiner DB (2014b) Protective immunity to H7N9 influenza viruses elicited by synthetic DNA vaccine. Vaccine 32(24):2833–2842. doi:10.1016/j.vaccine.2014.02.038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yersal O, Barutca S (2014) Biological subtypes of breast cancer: prognostic and therapeutic implications. World J Clin Oncol 5(3):412–424. doi:10.5306/wjco.v5.i3.412

    Article  PubMed  PubMed Central  Google Scholar 

  • Zaks K, Jordan M, Guth A, Sellins K, Kedl R, Izzo A, Bosio C, Dow S (2006) Efficient immunization and cross-priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes. J Immunol (Baltimore, Md: 1950) 176 (12):7335–7345

    Google Scholar 

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Authors and Affiliations

  1. Inovio Pharmaceuticals, 660 W. Germantown Pike, Suite 110, Plymouth Meeting, PA, 19462, USA

    Kimberly A. Kraynyak, Angela Bodles-Brakhop & Mark Bagarazzi

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  1. Kimberly A. Kraynyak
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  2. Angela Bodles-Brakhop
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  3. Mark Bagarazzi
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Correspondence to Mark Bagarazzi .

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  1. Faculty of Medicine, Cancer Sciences Unit, University of Southampton, Southhampton, United Kingdom

    Natalia Savelyeva

  2. Faculty of Medicine, Cancer Sciences Unit, University of Southampton , Southampton, United Kingdom

    Christian Ottensmeier

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Kraynyak, K.A., Bodles-Brakhop, A., Bagarazzi, M. (2015). Tapping the Potential of DNA Delivery with Electroporation for Cancer Immunotherapy. In: Savelyeva, N., Ottensmeier, C. (eds) Cancer Vaccines. Current Topics in Microbiology and Immunology, vol 405. Springer, Cham. https://doi.org/10.1007/82_2015_431

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