Human papillomavirus therapeutic vaccines: Targeting viral antigens as immunotherapy for precancerous disease and cancer

Expert Review of Vaccines

Volumn 12, Issue 3, 2013, Pages 271-283

  Morrow, Matthew P ^a   Yan, Jian ^a   Sardesai, Niranjan Y ^a  

^a Inovio Pharmaceuticals Inc   (United States)

Author keywords

cervical cancer; CIN2 3; HPV immunotherapy; therapeutic vaccine

Indexed keywords

PROTEIN E6; PROTEIN E7; VIRUS ANTIGEN; WART VIRUS VACCINE;

ANUS CANCER; ANUS CARCINOMA; GENETIC VARIABILITY; HEAD AND NECK CANCER; HUMAN; HUMAN PAPILLOMAVIRUS TYPE 16; HUMAN PAPILLOMAVIRUS TYPE 18; HUMAN PAPILLOMAVIRUS TYPE 6; IMMUNOTHERAPY; NEOPLASM; NONHUMAN; PAPILLOMAVIRUS INFECTION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRECANCER; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; TH1 CELL; UTERINE CERVIX CANCER; UTERINE CERVIX CARCINOMA IN SITU;

CANCER VACCINES; CERVICAL INTRAEPITHELIAL NEOPLASIA; CLINICAL TRIALS AS TOPIC; FEMALE; HUMANS; IMMUNOTHERAPY, ACTIVE; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRUS INFECTIONS; PAPILLOMAVIRUS VACCINES; TREATMENT OUTCOME; UTERINE CERVICAL NEOPLASMS; VACCINATION;

EID: 84875196919     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/erv.13.23     Document Type: Review

References (101)

1. de Martel C, Ferlay J, Franceschi S et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 13(6), 607-615 (2012).
2. WHO - Department of Immunization, Vaccines and Biologicals. Human Papillomavirus and HPV Vaccines: Technical Information for Policymakers and Health Professionals. WHO Press, Geneva, Switzerland (2007).
3. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Cancer incidence and mortality worldwide. IARC CancerBase
4. CDC. Sexual transmitted disease treatment guidelines - human papillomavirus (HPV) infection. MMWR 59(RR12), 1-110 (2010).
5. Romanowski B. Long-term protection against cervical infection with the human papillomavirus: review of currently available vaccines. Hum. Vaccines 7(2), 161-169 (2011).
6. Smith JS, Lindsay L, Hoots B et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int. J. Cancer 121(3), 621-632 (2007).
7. Chan PJ, Seraj IM, Kalugdan TH, King A. Blastocysts exhibit preferential uptake of DNA fragments from the E6-E7 conserved region of the human papillomavirus. Gynecol. Oncol. 58(2), 194-197 (1995).
8. Muñoz N, Bosch FX, de Sanjosé S et al.; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N. Engl. J. Med. 348(6), 518-527 (2003).
9. Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine 24(Suppl. 1), S1-S15 (2006).
10. Chaturvedi AK, Engels EA, Pfeiffer RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J. Clin. Oncol. 29(32), 4294-4301 (2011).
11. Harper DM, Franco EL, Wheeler CM et al. 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(9518), 1247-1255 (2006).
12. Villa LL, Costa RL, Petta CA et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebocontrolled multicentre Phase II efficacy trial. Lancet Oncol. 5(6), 271-278 (2005).
13. Villa LL, Ault KA, Giuliano AR et al. Immunologic responses following administration of a vaccine targeting human papillomavirus types 6, 11, 16, and 18. Vaccine 7(24), 5571-5583 (2006).
14. Harper DM, Franco EL, Wheeler C et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 364(9447), 1757-1765 (2004).
15. Hildesheim A, Herrero R, Wacholder S et al. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection. JAMA 298(7), 743-753 (2007).
16. Goldstone SE, Vuocolo S. A prophylactic quadrivalent vaccine for the prevention of infection and disease related to HPV-6, -11, -16 and -18. Expert Rev. Vaccines 11(4), 395-406 (2012).
17. Miller DL, Puricelli MD, Stack MS. Virology and molecular pathogenesis of HPV (human papillomavirus)-associated oropharyngeal squamous cell carcinoma. Biochem. J. 443(2), 339-353 (2012).
18. Ibeanu OA. Molecular pathogenesis of cervical cancer. Cancer Biol. Ther. 11(3), 295-306 (2011).
19. Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnürch HG, zur Hausen H. Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc. Natl Acad. Sci. USA 80(2), 560-563 (1983).
20. Dürst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc. Natl Acad. Sci. USA 80(12), 3812-3815 (1983).
21. Ghittoni R, Accardi R, Hasan U, Gheit T, Sylla B, Tommasino M. The biological properties of E6 and E7 oncoproteins from human papillomaviruses. Virus Genes 40(1), 1-13 (2010).
22. Gillison ML, Koch WM, Capone RB et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J. Natl Cancer Inst. 92(9), 709-720 (2000).
23. Syrjänen S. Human papillomavirus (HPV) in head and neck cancer. J. Clin. Virol. 32(Suppl. 1), S59-S66 (2005).
24. Applebaum KM, Furniss CS, Zeka A et al. Lack of association of alcohol and tobacco with HPV16-associated head and neck cancer. J. Natl Cancer Inst. 99(23), 1801-1810 (2007).
25. Münger K, Scheffner M, Huibregtse JM, Howley PM. Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. Cancer Surv. 12, 197-217 (1992).
26. Darnell GA, Schroder WA, Antalis TM et al. Human papillomavirus E7 requires the protease calpain to degrade the retinoblastoma protein. J. Biol. Chem. 282(52), 37492-37500 (2007).
27. Ostor AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int. J. Gynecol. Pathol. 12, 186-192 (1993).
28. Firzlaff JM, Kiviat NB, Beckmann AM, Jenison SA, Galloway DA. Detection of human papillomavirus capsid antigens in various squamous epithelial lesions using antibodies directed against the L1 and L2 open reading frames. Virology 164(2), 467-477 (1988).
29. Petrovic D, Dempsey E, Doherty DG, Kelleher D, Long A. Hepatitis C virus - T-cell responses and viral escape mutations. Eur. J. Immunol. 42(1), 17-26 (2012).
30. Snyder CM. Buffered memory: a hypothesis for the maintenance of functional, virus-specific CD8(+) T cells during cytomegalovirus infection. Immunol. Res. 51(3), 195-204 (2011).
31. Haas A, Zimmermann K, Oxenius A. Antigen-dependent and -independent mechanisms of T and B cell hyperactivation during chronic HIV-1 infection. J. Virol. 85(23), 12102-121132011).
32. Williams LD, Bansal A, Sabbaj S et al. Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllers. J. Virol. 85(5), 2316-2324 (2011).
33. Fröhlich A, Kisielow J, Schmitz I et al. IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science 324(5934), 1576-1580 (2009).
34. Elsaesser H, Sauer K, Brooks DG. IL-21 is required to control chronic viral infection. Science 324(5934), 1569-1572 (2009).
35. Bonilla WV, Fröhlich A, Senn K et al. The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses. Science 335(6071), 984-989 (2012).
36. Ma B, Xu Y, Hung CF, Wu TC. HPV and therapeutic vaccines: where are we in 2010? Curr. Can. Ther. Rev. 6, 81-103 (2010).
37. van der Burg SH, Melief MC. Therapeutic vaccination against human papilloma virus induced malignancies. Curr. Opin. Immuol. 23(2), 252-257 (2011).
38. Su JH, Wu A, Scotney E et al. Immunotherapy for cervical cancer: research status and clinical potential. BioDrugs 24(2), 109-129 (2010).
39. Lin K, Roosinovich E, Ma B, Hung CF, Wu TC. Therapeutic HPV DNA vaccines. Immunol. Res. 47(1), 86-112 (2010).
40. Abastado JP. The next challenge in cancer immunotherapy: controlling T-cell traffic to the tumor. Cancer Res. 72(9), 109-129 (2012).
41. Bernatchez C, Radvanyi LG, Hwu P. Advances in the treatment of metastatic melanoma: adoptive T-cell therapy. Semin. Oncol. 39(2), 215-226 (2012).
42. van Duikeren S, Fransen MF, Redeker A et al. Vaccine-induced effector-memory CD8+ T cell responses predict therapeutic efficacy against tumors. J. Immuol. 189(7), 3397-3403 (2012).
43. Zhou Q, Schneider IC, Edes I et al. T cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing. Blood 120(22), 4334-4342 (2012).
44. Lesterhuis WJ, Haanen JB, Punt CJ. Cancer immunotherapy - revisited. Nat. Rev. Drug Disc. 10, 591-600 (2011).
45. Dillon S, Sasagawa T, Crawford A et al. Resolution of cervical dysplasia is associated with T-cell proliferative responses to human papillomavirus type 16 E2. J. Gen. Virol. (88), 803-813 (2007).
46. Øvestad IT, Gudlaugsson E, Skaland I et al. Local immune response in the microenvironment of CIN2-3 with and without spontaneous regression. Mod. Pathol. 23(9), 1231-1240 (2010).
47. Peng S, Trimble C, Wu L et al. HLADQB102-restricted HPV-16 E7 peptidespecific CD4+ T-cell immune responses correlate with regression of HPV-16- associated high-grade squamous intraepithelial lesions. Clin. Cancer Res. 13(8), 2479-2487 (2007).
48. Jung AC, Guihard S, Krugell S et al. CD8- alpha T-cell infiltration in human papillomavirus-related oropharyngeal carcinoma correlates with improved patient prognosis. Int. J. Cancer 132(2), E26-E36 (2012).
49. Kadish AS, Ho GY, Burk RD et al. Lymphoproliferative responses to human papillomavirus (HPV) type 16 proteins E6 and E7: outcome of HPV infection and associated neoplasia. J. Natl Cancer Inst. 89(17), 1285-1293 (1997).
50. Kadish AS, Timmins P, Wang Y et al. Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cellmediated immune responses to an HPV type 16 E7 peptide. Cancer Epidemiol. Biomarkers 11(5), 483-488 (2002).
51. Trimble CL, Clark RA, Thoburn C et al. Human papillomavirus 16-associated cervical intraepithelial neoplasia in humans excludes CD8 T cells from dysplastic epithelium. J. Immunol. 185(11), 7107-7114 (2010).
52. Welters MJ, Kenter GG, de Vos van Steenwijk et al. Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses. Proc. Natl Acad. Sci. USA 107(26), 11895-11899 (2010).
53. Sarkar AK, Tortolero-Luna G, Follen M, Sastry KJ. Inverse correlation of cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 with recurrence of cervical intraepithelial neoplasia in a cross-sectional study. Gynecol. Oncol. 99(3), 251-261 (2005).
54. Paavonen J, Jenkins D, Bosch FX et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a Phase III double-blind, randomised controlled trial. Lancet 369(9580), 2161-2170 (2007).
55. de Jong A, O'Neill T, Khan AY et al. Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16 L2E7E6 fusion protein vaccine. Vaccine 20(30), 3456-3464 (2002).
56. Thompson HS, Davies ML, Holding FP et al. Phase I safety and antigenicity of TA-GW: a recombinant HPV6 L2E7 vaccine for the treatment of genital warts. Vaccine 17(1), 40-49 (1999).
57. Borysiewicz LK, Fianders A, Nimako M et al. A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. Lancet 347(9014), 1523-1527 (1996).
58. García-Hernández E, González-Sánchez J, Andrade-Manzano A et al. Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with P < E2 recombinant vaccine. Cancer Gene Ther. 13(6), 592-597 (2006).
59. Ferrara A, Nonn M, Schreckenberger C et al. Dendritic cell-based tumor vaccine for cervical cancer II: results of a clinical pilot study in 15 individual patients. J. Cancer Res. Clin. Oncol. 129(9), 521-530 (2003).
60. Santin AD, Bellone S, Gokden M, Cannon MJ, Parham GP. Vaccination with HPV-18 E7-pulsed dendritic cells in a patient with metastatic cervical cancer. N. Engl. J. Med. 346(22), 1752-1753 (2002).
61. Santin AD, Bellone S, Palmieri M et al. HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities. Gynecol. Oncol. 100(3), 469-478 (2006).
62. Lamains LA. The biology of human papillomaviruses: from warts to cancer. Infect. Agents Dis. 2(2), 74-86 (1993).
63. Burd EM. Human papillomavirus and cervical cancer. Clin. Microbiol. Rev. 16(1), 1-17 (2003).
64. Zur Hausen H. Papillomavirus infections - a major cause of human cancers. Biochim. Biophys. Acta 1288(2), 55-78 (1996).
65. Jabbar SF, Park S, Schweizer J et al. Cervical cancers require the continuous expression of the human papillomavirus type 16 e7 oncoprotein even in the presence of the viral e6 oncoprotein. Cancer Res. 72(16), 4008-4016 (2012).
66. Duensing S, Lee LY, Duensing A et al. The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc. Natl Acad. Sci. USA 97(18), 10002-10007 (2000).
67. Moore RA, Walcott S, White KL et al. Therapeutic immunisation with COPV early genes by epithelial DNA delivery. Virology 314(2), 630-635 (2003).
68. Moore RA, Santos EB, Nicholls PK et al. Intraepithelial DNA immunisation with a plasmid encoding a codon optimised COPV E1 gene sequence, but not the wildtype gene sequence completely protects against mucosal challenge with infectious COPV in beagles. Virology 304(2), 451-459 (2002).
69. Gutierrez C, Tinoco A, Navarro T et al. Therapeutic vaccination with P < E2 can eliminate precancerous lesions (CIN1, CIN2 and CIN3) associated with infection by oncogenic human papillomavirus. Hum. Gene Ther. 15(5), 421-431 (2004).
70. Yim EK, Park JS. The role of HPV E6 and E7 oncoproteins in HPV-associated cervical carcinogenesis. Cancer Res. Treat. 37(6), 319-324 (2005).
71. Yan J, Harris K, Khan AS, Draghia-Akli R, Sewell D, Weiner DB. 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 (2008).
72. Sharma C, Dey B, Wehiduzzaman M, Singh N. Human papillomavirus 16 L1-E7 chimeric virus like particles show prophylactic and therapeutic efficacy in murine model of cervical cancer. Vaccine 5417-5424 (2012).
73. Muderspach L, Wilczynski S, Roman L et al. A Phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high-grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive. Clin. Cancer Res. 6(9), 3406-3416 (2000).
74. Steller MA, Gurski KJ, Murakami M et al. Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7. Clin. Cancer Res. 4(9), 2103-2109 (1998).
75. van Driel WJ, Ressing ME, Kenter GG et al. Vaccination with HPV16 peptides of patients with advanced cervical carcinoma: clinical evaluation of a Phase I-II trial. Eur. J. Cancer 35(6), 946-952 (1999).
76. Trimble CL, Peng S, Kos F et al. A Phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin. Cancer Res. 15(1), 361-367 (2009).
77. Hallez S, Simon P, Maudoux F et al. Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia. Cancer Immunol. Immunother. 53(7), 642-650 (2004).
78. Einstein MH, Kadish AS, Burk RD et al. Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III. Gynecol. Oncol. 106(3), 453-460 (2007).
79. Van Doorslaer K, Reimers LL, Studentsov YY, Einstein MH, Burk RD. Serological response to an HPV16 E7 based therapeutic vaccine in women with highgrade cervical dysplasia. Gynecol. Oncol. 116(2), 208-212 (2010).
80. Sheets EE, Urban RG, Crum CP et al. Immunotherapy of human cervical high-grade cervical intraepithelial neoplasia with microparticle-delivered human papillomavirus 16 E7 plasmid DNA. Am. J. Obstet. Gynecol. 188(4), 916-926 (2003).
81. Welters MJ, Kenter GG, Piersma SJ et al. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin. Cancer Res. 14(1), 178-187 (2008).
82. Kenter GG, Welters MJ, Valentijn AR et al. Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity. Clin. Cancer Res. 14(1), 169-177 (2008).
83. Kaufmann AM, Stern PL, Rankin EM et al. Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer. Clin. Cancer Res. 8(12), 3676-3685 (2002).
84. Migueles SA, Osborne CM, Royce C et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity 29(6), 1009-1021 (2008).
85. Migueles SA, Rood JE, Berkley AM et al. Trivalent adenovirus type 5 HIV recombinant vaccine primes for modest cytotoxic capacity that is greatest in humans with protective HLA class I alleles. PLoS Pathog. 7(2), e1002002 (2001).
86. Lowin B, Hahne M, Mattmann C, Tschopp J. Cytolytic T-cell cytoxicity is mediated through perforin and Fas lytic pathways. Nature 370(6491), 650-652 (1994).
87. Zaritskaya L, Shurin MR, Sayers TJ, Malyguine AM. New flow cytometric assays for monitoring cell-mediated cytotoxicity. Expert Rev. Vaccines 9(6), 601-616 (2010).
88. Bagarazzi ML, Yan J, Morrow MP et al. Immunotherapy against HPV 16/18 generates potent Th1 and cytotoxic cellular immune responses. Sci. Transl. Med. 4(155), 155ra138 (2012).
89. Varadarajan N, Julg B, Yamanaka YJ et al. A high-throughput single-cell analysis of human CD8+ T cell functions reveals discordance for cytokine secretion and cytolysis. J. Clin. Invest. 121(11), 4322-4331 (2011).
90. Alexandrescu DT, Ichim TE, Riordan NH et al. Immunotherapy for melanoma: current status and perspectives. J. Immunother. 33(6), 570-590 (2010).
91. Schiffman M, Solomon D. Findings to date from the ASCUS-LSIL Triage Study (ALTS). Arch. Pathol. Lab. Med. 127, 946-949 (2003).
92. Kenter GG, Welters MJP, Valentjin R et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N. Engl. J. Med. 361, 1838-1847 (2009).
93. WHO. Sexual and reproductive health. Cervical cancer, human papillomavirus (HPV) and HPV vaccines. www.who.int/reproductivehealth/ publications/cancers/RHR-08-14/en/ index.html
94. WHO. International Agency for Research on Cancer. GLOBOCAN 2008. http://globocan.iarc.fr
95. CDC. HPV 2010 STD Treatment Guidelines. www.cdc.gov/std/treatment/2010/ hpv.htm
96. CDC press release. National survey shows HPV vaccine rates trail other teen vaccines. www.cdc.gov/media/releases/2011/p0825- hpv-vaccine.html
97. EMA. Annex I Summary of Product Characteristics for the HPV Vaccine 'Gardasil' 2008. Updated 2012. www.ema.europa.eu/docs/en-GB/ document-library/EPAR-Product- Information/human/000703/ WC500021142.pdf
98. Transgene announces positive Phase II results for its HPV therapeutic vaccine in precancerous cervical lesions. www.transgene.fr/images/stories/en/ pdf/ communique-presse/communiques- divers-2006/CP-US%20Eurogin%20 25-04-06.pdf
99. Transgene reports randomized Phase 2b data with its therapeutic HPV vaccine TG4001 in women with CIN2/3 intraepithelial cervical neoplasia. www.transgene.fr/index.php?option=com- press-release&task=download&id= 208&l =en
100. CDC. Sexually transmitted diseases. Genital HPV infection - fact sheet. www.cdc.gov/std/hpv/stdfact-hpv.htm
101. CDC. www.cdc.gov