Therapeutic HPV DNA vaccines

Immunologic Research

Volumn 47, Issue 1-3, 2010, Pages 86-112

  Lin, Ken ^a   Roosinovich, Elena ^b   Ma, Barbara ^c   Hung, Chien Fu ^c,d   Wu, T C ^c,d  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d DEPARTMENT OF PATHOLOGY   (United States)

Author keywords

Cervical cancer; DNA vaccines; HPV; HPV E6; HPV E7; Therapeutic vaccine

Indexed keywords

APIGENIN; BORTEZOMIB; CALRETICULIN; CISPLATIN; DNA VACCINE; EPIGALLOCATECHIN GALLATE; GALECTIN 1; GLYCOPROTEIN GP 96; HEAT SHOCK PROTEIN 70; INDOLEAMINE 2,3 DIOXYGENASE; INTERLEUKIN 10; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PROGRAMMED DEATH 1 LIGAND 1; PROTEASOME; STAT3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; VIRUS CAPSID ANTIGEN; WART VIRUS VACCINE; CANCER VACCINE; ONCOPROTEIN; VIRUS ANTIGEN;

ANTIGEN BINDING; ANTIGEN EXPRESSION; ANTIGEN SPECIFICITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL INTERACTION; CELL SURVIVAL; CELLULAR IMMUNITY; CODON; DENDRITIC CELL; DNA IMMUNIZATION; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG MANUFACTURE; DRUG SAFETY; DRUG STABILITY; DRUG TOLERABILITY; ENDOPLASMIC RETICULUM; GENE GUN; HEAD AND NECK CARCINOMA; HELPER CELL; HUMAN; HUMAN PAPILLOMAVIRUS TYPE 16; HUMORAL IMMUNITY; IMMUNOMODULATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW; SQUAMOUS CELL CARCINOMA; T LYMPHOCYTE ACTIVATION; TUMOR CELL; VIRUS LIKE AGENT; CLINICAL TRIAL (TOPIC); FEMALE; GENETICS; IMMUNOLOGY; METABOLISM; PAPILLOMA VIRUS; PAPILLOMAVIRUS INFECTIONS; UTERINE CERVICAL NEOPLASMS;

ANTIGENS, VIRAL; CANCER VACCINES; CLINICAL TRIALS AS TOPIC; DENDRITIC CELLS; FEMALE; HUMANS; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRIDAE; PAPILLOMAVIRUS INFECTIONS; PAPILLOMAVIRUS VACCINES; UTERINE CERVICAL NEOPLASMS; VACCINES, DNA;

EID: 77953958731     PISSN: 0257277X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s12026-009-8141-6     Document Type: Review

References (121)

1. DM Parkin F Bray J Ferlay P Pisani 2005 Global cancer statistics, 2002 CA Cancer J Clin 55 74 108 15761078
2. JM Walboomers MV Jacobs MM Manos FX Bosch JA Kummer KV Shah, et al. 1999 Human papillomavirus is a necessary cause of invasive cervical cancer worldwide J Pathol 189 12 19 10451482
3. JS Smith L Lindsay B Hoots J Keys S Franceschi R Winer, et al. 2007 Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update Int J Cancer 121 621 632 17405118
4. EM de Villiers C Fauquet TR Broker HU Bernard H zur Hausen 2004 Classification of papillomaviruses Virology 324 17 27 15183049
5. RW Tindle 2002 Immune evasion in human papillomavirus-associated cervical cancer Nat Rev Cancer 2 59 65 11902586
6. H zur Hausen 2002 Papillomaviruses and cancer: from basic studies to clinical application Nat Rev Cancer 2 342 350 12044010
7. R Roden TC Wu 2006 How will HPV vaccines affect cervical cancer? Nat Rev Cancer 6 753 763 16990853
8. RB Roden A Monie TC Wu 2007 Opportunities to improve the prevention and treatment of cervical cancer Curr Mol Med 7 490 503 17691964
9. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356:1915-27.
10. SM Garland M Hernandez-Avila CM Wheeler G Perez DM Harper S Leodolter, et al. 2007 Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases N Engl J Med 356 1928 1943 17494926 (Pubitemid 46740303)
11. DM Harper EL Franco CM Wheeler AB Moscicki B Romanowski CM Roteli-Martins, et al. 2006 Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial Lancet 367 1247 1255 16631880
12. LL Villa RL Costa CA Petta RP Andrade KA Ault AR Giuliano, et al. 2005 Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial Lancet Oncol 6 271 278 15863374
13. LL Villa KA Ault AR Giuliano RL Costa CA Petta RP Andrade, et al. 2006 Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18 Vaccine 24 5571 5583 16753240
14. JT Schiller X Castellsague LL Villa A Hildesheim 2008 An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results Vaccine 26 Suppl 10 K53 K61 18847557
15. CF Hung B Ma A Monie SW Tsen TC Wu 2008 Therapeutic human papillomavirus vaccines: current clinical trials and future directions Expert Opin Biol Ther 8 421 439 18352847
16. HL Greenstone JD Nieland KE de Visser ML De Bruijn R Kirnbauer RB Roden, et al. 1998 Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model Proc Natl Acad Sci USA 95 1800 1805 9465097
17. S Peng IH Frazer GJ Fernando J Zhou 1998 Papillomavirus virus-like particles can deliver defined CTL epitopes to the MHC class I pathway Virology 240 147 157 9448699
18. K Schafer M Muller S Faath A Henn W Osen H Zentgraf, et al. 1999 Immune response to human papillomavirus 16 L1E7 chimeric virus-like particles: induction of cytotoxic T cells and specific tumor protection Int J Cancer 81 881 888 10362134
19. SC Fausch DM Da Silva GL Eiben IC Le Poole WM Kast 2003 HPV protein/peptide vaccines: from animal models to clinical trials Front Biosci 8 s81 s91 12456298
20. CM Gerard N Baudson K Kraemer C Bruck N Garcon Y Paterson, et al. 2001 Therapeutic potential of protein and adjuvant vaccinations on tumour growth Vaccine 19 2583 2589 11257396
21. CW Lin JY Lee YP Tsao CP Shen HC Lai SL Chen 2002 Oral vaccination with recombinant Listeria monocytogenes expressing human papillomavirus type 16 E7 can cause tumor growth in mice to regress Int J Cancer 102 629 637 12448006
22. GR Gunn A Zubair C Peters ZK Pan TC Wu Y Paterson 2001 Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumours immortalized by HPV-16 J Immunol 167 6471 6479 11714814
23. IA Jabbar GJ Fernando N Saunders A Aldovini R Young K Malcolm, et al. 2000 Immune responses induced by BCG recombinant for human papillomavirus L1 and E7 proteins Vaccine 18 2444 2453 10738102
24. JJ Donnelly JB Ulmer MA Liu 1997 DNA vaccines Life Sci 60 163 172 9000640
25. S Gurunathan DM Klinman RA Seder 2000 DNA vaccines: immunology, application, and optimization Annu Rev Immunol 18 927 974 10837079
26. C Trimble CT Lin CF Hung S Pai J Juang L He, et al. 2003 Comparison of the CD8+ T cell responses and antitumor effects generated by DNA vaccine administered through gene gun, biojector, and syringe Vaccine 21 4036 4042 12922140
27. CA Chen MC Chang WZ Sun YL Chen YC Chiang CY Hsieh, et al. 2009 Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects Gene Ther 16 776 787 19357714
28. A Luxembourg CF Evans D Hannaman 2007 Electroporation-based DNA immunisation: translation to the clinic Expert Opin Biol Ther 7 1647 1664 17961089
29. AK Roos F Eriksson JA Timmons J Gerhardt U Nyman L Gudmundsdotter, et al. 2009 Skin electroporation: effects on transgene expression, DNA persistence, local tissue environment PLoS One 4 e7226 19789652
30. AK Roos F Eriksson DC Walters P Pisa AD King 2009 Optimization of skin electroporation in mice to increase tolerability of DNA vaccine delivery to patients Mol Ther 17 1637 1642 19532140
31. SR Best S Peng CM Juang CF Hung D Hannaman JR Saunders, et al. 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 5450 5459 19622402
32. SH Seo HT Jin SH Park JI Youn YC Sung 2009 Optimal induction of HPV DNA vaccine-induced CD8(+) T cell responses and therapeutic antitumor effect by antigen engineering and electroporation Vaccine 27 5906 5912 19651174
33. J Yan K Harris AS Khan R Draghia-Akli D Sewell DB Weiner 2008 Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques Vaccine 26 5210 5215 18455277
34. VGX pharmaceuticals, Inc. Phase I of human papillomavirus (HPV) DNA plasmid (VGX-3100) + Electroporation for CIN 2 or 3 [Clinicaltrials.gov identifier NCT00685412]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov. Accessed 2009 October 13.
35. S Mehier-Humbert RH Guy 2005 Physical methods for gene transfer: improving the kinetics of gene delivery into cells Adv Drug Deliv Rev 57 733 753 15757758
36. E Zeira A Manevitch Z Manevitch E Kedar M Gropp N Daudi, et al. 2007 Femtosecond laser: a new intradermal DNA delivery method for efficient, long-term gene expression and genetic immunization Faseb J 21 3522 3533 17575264
37. SW Tsen CY Wu A Meneshian SI Pai CF Hung TC Wu 2009 Femtosecond laser treatment enhances DNA transfection efficiency in vivo J Biomed Sci 16 36 19338665
38. ML Hedley J Curley R Urban 1998 Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses Nat Med 4 365 368 9500615
39. B Klencke M Matijevic RG Urban JL Lathey ML Hedley M Berry, et al. 2002 Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal dysplasia: a phase I study of ZYC101 Clin Cancer Res 8 1028 1037 12006515
40. H Storrie DJ Mooney 2006 Sustained delivery of plasmid DNA from polymeric scaffolds for tissue engineering Adv Drug Deliv Rev 58 500 514 16759734
41. EE Sheets RG Urban CP Crum ML Hedley JA Politch MA Gold, et al. 2003 Immunotherapy of human cervical high-grade cervical intraepithelial neoplasia with microparticle-delivered human papillomavirus 16 E7 plasmid DNA Am J Obstet Gynecol 188 916 926 12712086
42. F Garcia KU Petry L Muderspach MA Gold P Braly CP Crum, et al. 2004 ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial Obstet Gynecol 103 317 326 14754702
43. JH van den Berg B Nujien JH Beijnen A Vincent H van Tinteren J Kluge, et al. 2009 Optimization of intradermal vaccination by DNA tattooing in human skin Hum Gene Ther 20 181 189 19301471
44. D Pokorna I Rubio M Muller 2008 DNA-vaccination via tattooing induces stronger humoral and cellular immune responses than intramuscular delivery supported by molecular adjuvants Genet Vaccines Ther 6 4 18257910
45. Su X, Kim BS, Kim SR, Hammond PT, Irvine DJ. Layer-by-Layer-assembled multilayer films for transcutaneous drug and vaccine delivery. ACS Nano. 2009 Oct 13.
46. MR Prausnitz JA Mikszta M Cormier AK Andrianov 2009 Microneedle-based vaccines Curr Top Microbiol Immunol 333 369 393 19768415
47. R Voltan A Castaldello E Brocca-Cofano R De Michele C Triulzi G Altavilla, et al. 2009 Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice Vaccine 27 4498 4507 19450649
48. G Elliott P O'Hare 1997 Intercellular trafficking and protein delivery by a herpesvirus structural protein Cell 88 223 233 9008163
49. A Phelan G Elliott P O'Hare 1998 Intercellular delivery of functional p53 by the herpesvirus protein VP22 Nat Biotechnol 16 440 443 9592391
50. MS Dilber A Phelan A Aints AJ Mohamed G Elliott CI Smith, et al. 1999 Intercellular delivery of thymidine kinase prodrug activating enzyme by the herpes simplex virus protein, VP22 Gene Ther 6 12 21 10341871
51. WA Wybranietz CD Gross A Phelan P O'Hare M Spiegel F Graepler, et al. 2001 Enhanced suicide gene effect by adenoviral transduction of a VP22-cytosine deaminase (CD) fusion gene Gene Ther 8 1654 1664 11895004
52. M Lundberg M Johansson 2001 Is VP22 nuclear homing an artifact? Nat Biotechnol 19 713 714 11479552
53. TW Kim CF Hung JW Kim J Juang PJ Chen L He, et al. 2004 Vaccination with a DNA vaccine encoding herpes simplex virus type 1 VP22 linked to antigen generates long-term antigen-specific CD8-positive memory T cells and protective immunity Hum Gene Ther 15 167 177 14975189
54. CF Hung WF Cheng CY Chai KF Hsu L He M Ling, et al. 2001 Improving vaccine potency through intercellular spreading and enhanced MHC class I presentation of antigen J Immunol 166 5733 5740 11313416
55. S Peng C Trimble H Ji L He YC Tsai B Macaes, et al. 2005 Characterization of HPV-16 E6 DNA vaccines employing intracellular targeting and intercellular spreading strategies J Biomed Sci 12 689 700 16200349
56. CF Hung L He J Juang TJ Lin M Ling TC Wu 2002 Improving DNA vaccine potency by linking Marek's disease virus type 1 VP22 to an antigen J Virol 76 2676 2682 11861834
57. CF Zheng R Brownlie DY Huang LA Babiuk S den Hurk 2006 Intercellular trafficking of the major tegument protein VP22 of bovine herpesvirus-1 and its application to improve a DNA vaccine Arch Virol 151 985 993 16374718
58. C Zheng LA Babiuk S den Hurk 2005 Bovine herpesvirus 1 VP22 enhances the efficacy of a DNA vaccine in cattle J Virol 79 1948 1953 15650221
59. N Onai A Obata-Onai MA Schmid MG Manz 2007 Flt3 in regulation of type I interferon-producing cell and dendritic cell development Ann N Y Acad Sci 1106 253 261 17360795
60. MR Shurin PP Pandharipande TD Zorina C Haluszczak VM Subbotin O Hunter, et al. 1997 FLT3 ligand induces the generation of functionally active dendritic cells in mice Cell Immunol 179 174 184 9268501
61. CF Hung KF Hsu WF Cheng CY Chai L He M Ling, et al. 2001 Enhancement of DNA vaccine potency by linkage of antigen gene to a gene encoding the extracellular domain of Fms-like tyrosine kinase 3-ligand Cancer Res 61 1080 1088 11221836
62. FU Hartl M Hayer-Hartl 2002 Molecular chaperones in the cytosol: from nascent chain to folded protein Science 295 1852 1858 11884745
63. MJ Pandya H Bendz F Manzenrieder E Noessner H Kessler J Buchner, et al. 2009 Interaction of human heat shock protein 70 with tumor-associated peptides Biol Chem 390 305 312 19199830
64. RM Vabulas P Ahmad-Nejad S Ghose CJ Kirschning RD Issels H Wagner 2002 HSP70 as endogenous stimulus of the toll/interleukin-1 receptor signal pathway J Biol Chem 277 15107 15112 11842086
65. CL Trimble S Peng F Kos P Gravitt R Viscidi E Sugar, et al. 2009 A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3 Clin Cancer Res 15 361 367 19118066
66. Johns Hopkins University. Vaccine therapy with or without imiquimod in treating patients with grade 3 cervical intraepithelial neoplasia [ClinicalTrials.gov identifier NCT00788164]. US Natioanl Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov. Accessed 2009 June 4.
67. M Le Borgne N Etchart A Goubier SA Lira JC Sirard N van Rooijen, et al. 2006 Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo Immunity 24 191 201 16473831
68. Kang TH, Chung JY, Monie A, Pai SI, Hung CF, Wu TC. Enhancing DNA vaccine potency by co-administration of xenogenic MHC-class-I DNA. Gene Ther. 2009 (in press).
69. CW Tseng CF Hung RD Alvarez C Trimble WK Huh D Kim, et al. 2008 Pretreatment with cisplatin enhances E7-specific CD8+ T-Cell-mediated antitumor immunity induced by DNA vaccination Clin Cancer Res 14 3185 3192 18483387
70. CW Tseng A Monie CY Wu B Huang MC Wang CF Hung, et al. 2008 Treatment with proteasome inhibitor bortezomib enhances antigen-specific CD8+ T-cell-mediated antitumor immunity induced by DNA vaccination J Mol Med 86 899 908 18542898
71. TH Kang JH Lee CK Song HD Han BC Shin SI Pai, et al. 2007 Epigallocatechin-3-gallate enhances CD8+ T cell-mediated antitumor immunity induced by DNA vaccination Cancer Res 67 802 811 17234792
72. CM Chuang A Monie A Wu CF Hung 2009 Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects J Biomed Sci 16 49 19473507
73. CW Tseng A Monie C Trimble RD Alvarez WK Huh DJ Buchsbaum, et al. 2008 Combination of treatment with death receptor 5-specific antibody with therapeutic HPV DNA vaccination generates enhanced therapeutic anti-tumor effects Vaccine 26 4314 4319 18598733
74. CW Tseng C Trimble Q Zeng A Monie RD Alvarez WK Huh, et al. 2009 Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts Cancer Immunol Immunother 58 737 748 18815785
75. SN Stacey D Jordan AJ Williamson M Brown JH Coote JR Arrand 2000 Leaky scanning is the predominant mechanism for translation of human papillomavirus type 16 E7 oncoprotein from E6/E7 bicistronic mRNA J Virol 74 7284 7297 10906182
76. CT Lin YC Tsai L He R Calizo HH Chou TC Chang, et al. 2006 A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity J Biomed Sci 13 481 488 16649071
77. A Cid-Arregui V Juarez H zur Hausen 2003 A synthetic E7 gene of human papillomavirus type 16 that yields enhanced expression of the protein in mammalian cells and is useful for DNA immunization studies J Virol 77 4928 4937 12663798
78. J Yan DK Reichenbach N Corbitt DA Hokey MP Ramanathan KA McKinney, et al. 2009 Induction of antitumor immunity in vivo following delivery of a novel HPV-16 DNA vaccine encoding an E6/E7 fusion antigen Vaccine 27 431 440 19022315
79. Y Hirasawa M Arai F Imazeki M Tada R Mikata K Fukai, et al. 2006 Methylation status of genes upregulated by demethylating agent 5-aza-2′-deoxycytidine in hepatocellular carcinoma Oncology 71 77 85 17341888
80. M Arai F Imazeki Y Sakai R Mikata M Tada N Seki, et al. 2008 Analysis of the methylation status of genes up-regulated by the demethylating agent, 5-aza-2′-deoxycytidine, in esophageal squamous cell carcinoma Oncol Rep 20 405 412 18636205
81. D Lu T Hoory A Monie A Wu MC Wang CF Hung 2009 Treatment with demethylating agent, 5-aza-2′-deoxycytidine enhances therapeutic HPV DNA vaccine potency Vaccine 27 4363 4369 19481843
82. D Kim T Hoory A Monie JP Ting CF Hung TC Wu 2008 Enhancement of DNA vaccine potency through coadministration of CIITA DNA with DNA vaccines via gene gun J Immunol 180 7019 7027 18453624
83. EP Grant MT Michalek AL Goldberg KL Rock 1995 Rate of antigen degradation by the ubiquitin-proteasome pathway influences MHC class I presentation J Immunol 155 3750 3758 7561079
84. S Massa P Simeone A Muller E Benvenuto A Venuti R Franconi 2008 Antitumor activity of DNA vaccines based on the human papillomavirus-16 E7 protein genetically fused to a plant virus coat protein Hum Gene Ther 19 354 364 18439124
85. CF Hung WF Cheng L He M Ling J Juang CT Lin, et al. 2003 Enhancing major histocompatibility complex class I antigen presentation by targeting antigen to centrosomes Cancer Res 63 2393 2398 12750257
86. M Smahel I Polakova D Pokorna V Ludvikova M Duskova J Vlasak 2008 Enhancement of T cell-mediated and humoral immunity of beta-glucuronidase-based DNA vaccines against HPV16 E7 oncoprotein Int J Oncol 33 93 101 18575754
87. WF Cheng CF Hung CY Chai KF Hsu L He M Ling, et al. 2001 Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen J Clin Invest 108 669 678 11544272 (Pubitemid 32906195)
88. JW Kim CF Hung J Juang L He TW Kim DK Armstrong, et al. 2004 Comparison of HPV DNA vaccines employing intracellular targeting strategies Gene Ther 11 1011 1018 14985791
89. D Kim R Gambhira B Karanam A Monie CF Hung R Roden, et al. 2008 Generation and characterization of a preventive and therapeutic HPV DNA vaccine Vaccine 26 351 360 18096279
90. CF Hung WF Cheng KF Hsu CY Chai L He M Ling, et al. 2001 Cancer immunotherapy using a DNA vaccine encoding the translocation domain of a bacterial toxin linked to a tumor antigen Cancer Res 61 3698 3703 11325841
91. CT Lin TC Chang SW Shaw PJ Cheng CT Huang A Chao, et al. 2006 Maintenance of CD8 effector T cells by CD4 helper T cells eradicates growing tumors and promotes long-term tumor immunity Vaccine 24 6199 6207 16824651
92. F Castellino RN Germain 2006 Cooperation between CD4+ and CD8+ T cells: when, where, and how Annu Rev Immunol 24 519 540 16551258
93. TC Wu FG Guarnieri KF Staveley-O'Carroll RP Viscidi HI Levitsky L Hedrick, et al. 1995 Engineering an intracellular pathway for major histocompatibility complex class II presentation of antigens Proc Natl Acad Sci USA 92 11671 11675 8524826
94. H Ji TL Wang CH Chen SI Pai CF Hung KY Lin, et al. 1999 Targeting human papillomavirus type 16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine human papillomavirus type 16 E7-expressing tumors Hum Gene Ther 10 2727 2740 10584920
95. CH Huang S Peng L He YC Tsai DA Boyd TH Hansen, et al. 2005 Cancer immunotherapy using a DNA vaccine encoding a single-chain trimer of MHC class I linked to an HPV-16 E6 immunodominant CTL epitope Gene Ther 12 1180 1186 15800656
96. TW Kim CF Hung M Ling J Juang L He JM Hardwick, et al. 2003 Enhancing DNA vaccine potency by coadministration of DNA encoding antiapoptotic proteins J Clin Invest 112 109 117 12840065
97. WF Cheng MC Chang WZ Sun CN Lee HW Lin YN Su, et al. 2008 Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism Gene Ther 15 1007 1016 18356819
98. TW Kim JH Lee L He DA Boyd JM Hardwick CF Hung, et al. 2005 Modification of professional antigen-presenting cells with small interfering RNA in vivo to enhance cancer vaccine potency Cancer Res 65 309 316 15665308
99. B Huang CP Mao S Peng CF Hung TC Wu 2008 RNA interference-mediated in vivo silencing of Fas ligand as a strategy for the enhancement of DNA vaccine potency Hum Gene Ther 19 763 773 18627219
100. CF Hung YC Tsai L He TC Wu 2007 DNA vaccines encoding Ii-PADRE generates potent PADRE-specific CD4+ T-cell immune responses and enhances vaccine potency Mol Ther 15 1211 1219 17356542
101. P Cresswell 1994 Assembly, transport, and function of MHC class II molecules Annu Rev Immunol 12 259 293 8011283 (Pubitemid 24140416)
102. D Kim A Monie L He YC Tsai CF Hung TC Wu 2008 Role of IL-2 secreted by PADRE-specific CD4+ T cells in enhancing E7-specific CD8+ T-cell immune responses Gene Ther 15 677 687 18273057
103. D Kim T Hoory TC Wu CF Hung 2007 Enhancing DNA vaccine potency by combining a strategy to prolong dendritic cell life and intracellular targeting strategies with a strategy to boost CD4+ T cell Hum Gene Ther 18 1129 1139 17939748
104. D Kim A Monie YC Tsai L He MC Wang CF Hung, et al. 2008 Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice Gene Ther 15 1176 1183 18463686
105. P Ohlschlager M Quetting G Alvarez M Durst L Gissmann AM Kaufmann 2009 Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants Int J Cancer 125 189 198 19358269
106. S Akira K Takeda 2004 Toll-like receptor signalling Nat Rev Immunol 4 7 499 511 15229469
107. A Larange D Antonios M Pallardy S Kerdine-Romer 2009 TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation J Leukoc Biol 85 673 683 19164127
108. H Hemmi O Takeuchi T Kawai T Kaisho S Sato H Sanjo, et al. 2000 A Toll-like receptor recognizes bacterial DNA Nature 408 740 745 11130078
109. Y Kojima KQ Xin T Ooki K Hamajima T Oikawa K Shinoda, et al. 2002 Adjuvant effect of multi-CpG motifs on an HIV-1 DNA vaccine Vaccine 20 2857 2865 12126895
110. WS Alexander 2002 Suppressors of cytokine signalling (SOCS) in the immune system Nat Rev Immunol 2 410 416 12093007
111. XT Song K Evel-Kabler L Rollins M Aldrich F Gao XF Huang, et al. 2006 An alternative, effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells PLoS Med 3 e11 16381597
112. U Petrausch CH Poehlein SM Jensen C Twitty JA Thompson I Assmann, et al. 2009 Cancer immunotherapy: the role regulatory T cells play and what can be done to overcome their inhibitory effects Curr Mol Med 9 673 682 19689294
113. SJ Piersma ES Jordanova MI van Poelgeest KM Kwappenberg JM van der Hulst JW Drijfhout, et al. 2007 High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer Cancer Res 67 354 361 17210718
114. JW Molling TD de Gruijl J Glim M Moreno L Rozendaal CJ Meijer, et al. 2007 CD4(+)CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia Int J Cancer 121 1749 1755 17582606
115. M Beyer JL Schultze 2006 Regulatory T cells in cancer Blood 108 804 811 16861339
116. S Nair D Boczkowski M Fassnacht D Pisetsky E Gilboa 2007 Vaccination against the fork head family transcription factor Foxp3 enhances tumor immunity Cancer Res 67 371 380 17210720
117. CM Chuang T Hoory A Monie A Wu MC Wang CF Hung 2009 Enhancing therapeutic HPV DNA vaccine potency through depletion of CD4+ CD25+ T regulatory cells Vaccine 27 684 689 19056449
118. CH Chen TL Wang CF Hung Y Yang RA Young DM Pardoll, et al. 2000 Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene Cancer Res 60 1035 1042 10706121
119. AP Wlazlo H Deng W Giles-Davis HC Ertl 2004 DNA vaccines against the human papillomavirus type 16 E6 or E7 oncoproteins Cancer Gene Ther 11 457 464 15118761
120. S Rittich M Duskova J Mackova D Pokorna P Jinoch M Smahel 2005 Combined immunization with DNA and transduced tumor cells expressing mouse GM-CSF or IL-2 Oncol Rep 13 311 317 15643517
121. CG Drake E Jaffee DM Pardoll 2006 Mechanisms of immune evasion by tumors Adv Immunol 90 51 81 16730261