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A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC)

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Abstract

Background

We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

Methods

Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA).

Results

All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3.

Conclusions

AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

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Abbreviations

ELISA:

Enzyme-linked immunosorbent assay

ELISpot:

Enzyme-linked immunosorbent spot

HPV:

Human papillomavirus

HNC:

Head and neck cancer

IFNγ:

Interferon gamma

OPSCC:

Oropharyngeal squamous cell carcinoma

PBMC:

Peripheral blood mononuclear cells

TEAE:

Treatment emergent adverse events

References

  1. Arbyn M, Weiderpass E, Bruni L, de Sanjose S, Saraiya M, Ferlay J, Bray F (2020) Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health 8(2):e191–e203. https://doi.org/10.1016/S2214-109X(19)30482-6

    Article  PubMed  Google Scholar 

  2. Zhou C, Tuong ZK, Frazer IH (2019) Papillomavirus immune evasion strategies target the infected cell and the local immune system. Front Oncol 9:682. https://doi.org/10.3389/fonc.2019.00682

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chaturvedi AK, Engels EA, Anderson WF, Gillison ML (2008) Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 26(4):612–619. https://doi.org/10.1200/JCO.2007.14.1713

    Article  PubMed  Google Scholar 

  4. Hong A, Lee CS, Jones D, Veillard AS, Zhang M, Zhang X, Smee R, Corry J, Porceddu S, Milross C, Elliott M, Clark J, Rose B (2016) Rising prevalence of human papillomavirus-related oropharyngeal cancer in Australia over the last 2 decades. Head Neck 38(5):743–750. https://doi.org/10.1002/hed.23942

    Article  PubMed  Google Scholar 

  5. Welfare AIoHa (2017) Cancer in Australia 2017. AUstralian Institute of Health and Welfare, vol Cancer series no.101. Cat. no. CAN 100

  6. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29(32):4294–4301. https://doi.org/10.1200/JCO.2011.36.4596

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mahal BA, Catalano PJ, Haddad RI, Hanna GJ, Kass JI, Schoenfeld JD, Tishler RB, Margalit DN (2019) Incidence and demographic burden of HPV-associated oropharyngeal head and neck cancers in the United States. Cancer Epidemiol Biomarkers Prev 28(10):1660–1667. https://doi.org/10.1158/1055-9965.EPI-19-0038

    Article  PubMed  Google Scholar 

  8. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35. https://doi.org/10.1056/NEJMoa0912217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Moore EJ, Hinni ML (2013) Critical review: transoral laser microsurgery and robotic-assisted surgery for oropharynx cancer including human papillomavirus-related cancer. Int J Radiat Oncol Biol Phys 85(5):1163–1167. https://doi.org/10.1016/j.ijrobp.2012.08.033

    Article  PubMed  Google Scholar 

  10. Porceddu SV, Milne R, Brown E, Bernard A, Rahbari R, Cartmill B, Foote M, McGrath M, Coward J, Panizza B (2017) Validation of the ICON-S staging for HPV-associated oropharyngeal carcinoma using a pre-defined treatment policy. Oral Oncol 66:81–86. https://doi.org/10.1016/j.oraloncology.2017.01.002

    Article  PubMed  Google Scholar 

  11. Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867. https://doi.org/10.1056/NEJMoa1602252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, Jones CU, Dunlap NE, Seaward SA, Spencer S, Galloway TJ, Phan J, Dignam JJ, Le QT (2019) Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet 393(10166):40–50. https://doi.org/10.1016/S0140-6736(18)32779-X

    Article  CAS  PubMed  Google Scholar 

  13. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, Dalby M, Mistry P, Sen M, O'Toole L, Al Booz H, Dyker K, Moleron R, Whitaker S, Brennan S, Cook A, Griffin M, Aynsley E, Rolles M, De Winton E, Chan A, Srinivasan D, Nixon I, Grumett J, Leemans CR, Buter J, Henderson J, Harrington K, McConkey C, Gray A, Dunn J, De EHPVTG (2019) Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 393(10166):51–60. https://doi.org/10.1016/S0140-6736(18)32752-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Klaes R, Woerner SM, Ridder R, Wentzensen N, Duerst M, Schneider A, Lotz B, Melsheimer P, von Knebel DM (1999) Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes. Cancer Res 59(24):6132–6136

    CAS  PubMed  Google Scholar 

  15. Cheng MA, Farmer E, Huang C, Lin J, Hung CF, Wu TC (2018) Therapeutic DNA vaccines for human papillomavirus and associated diseases. Hum Gene Ther 29(9):971–996. https://doi.org/10.1089/hum.2017.197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chandra J, Dutton JL, Li B, Woo WP, Xu Y, Tolley LK, Yong M, Wells JW, G RL, Finlayson N, Frazer IH, (2017) DNA vaccine encoding HPV16 oncogenes E6 and E7 induces potent cell-mediated and humoral immunity which protects in tumor challenge and drives E7-expressing skin graft rejection. J Immunother 40(2):62–70. https://doi.org/10.1097/CJI.0000000000000156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chandra J, Woo WP, Dutton JL, Xu Y, Li B, Kinrade S, Druce J, Finlayson N, Griffin P, Laing KJ, Koelle DM, Frazer IH (2019) Immune responses to a HSV-2 polynucleotide immunotherapy COR-1 in HSV-2 positive subjects: a randomized double blinded phase I/IIa trial. PLoS ONE 14(12):e0226320. https://doi.org/10.1371/journal.pone.0226320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dutton JL, Woo WP, Chandra J, Xu Y, Li B, Finlayson N, Griffin P, Frazer IH (2016) An escalating dose study to assess the safety, tolerability and immunogenicity of a Herpes Simplex Virus DNA vaccine, COR-1. Hum Vaccin Immunother 12(12):3079–3088. https://doi.org/10.1080/21645515.2016.1221872

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tighiouart M, Rogatko A, Babb JS (2005) Flexible Bayesian methods for cancer phase I clinical trials. Dose escalation with overdose control. Stat Med 24(14):2183–2196. https://doi.org/10.1002/sim.2106

    Article  PubMed  Google Scholar 

  20. Fakhry C, Lacchetti C, Perez-Ordonez B (2018) Human papillomavirus testing in head and neck carcinomas: ASCO clinical practice guideline endorsement summary of the CAP guideline. J Oncol Pract 14(10):613–617. https://doi.org/10.1200/JOP.18.00433

    Article  PubMed  Google Scholar 

  21. Mirghani H, Casiraghi O, Guerlain J, Amen F, He MX, Ma XJ, Luo Y, Mourareau C, Drusch F, Lakdhar AB, Melkane A, St Guily L, Badoual C, Scoazec JY, Borget I, Auperin A, Dalstein V, Vielh P (2016) Diagnosis of HPV driven oropharyngeal cancers: comparing p16 based algorithms with the RNAscope HPV-test. Oral Oncol 62:101–108. https://doi.org/10.1016/j.oraloncology.2016.10.009

    Article  PubMed  Google Scholar 

  22. van der Burg SH, Ressing ME, Kwappenberg KM, de Jong A, Straathof K, de Jong J, Geluk A, van Meijgaarden KE, Franken KL, Ottenhoff TH, Fleuren GJ, Kenter G, Melief CJ, Offringa R (2001) Natural T-helper immunity against human papillomavirus type 16 (HPV16) E7-derived peptide epitopes in patients with HPV16-positive cervical lesions: identification of 3 human leukocyte antigen class II-restricted epitopes. Int J Cancer 91(5):612–618. https://doi.org/10.1002/1097-0215(200002)9999:9999<:aid-ijc1119>3.0.co;2-c

    Article  PubMed  Google Scholar 

  23. Paaso A, Koskimaa HM, Welters MJ, Grenman S, Syrjanen K, van der Burg SH, Syrjanen S (2015) Cell mediated immunity against HPV16 E2, E6 and E7 peptides in women with incident CIN and in constantly HPV-negative women followed-up for 10-years. J Transl Med 13:163. https://doi.org/10.1186/s12967-015-0498-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wargowski E, Johnson LE, Eickhoff JC, Delmastro L, Staab MJ, Liu G, McNeel DG (2018) Prime-boost vaccination targeting prostatic acid phosphatase (PAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) using Sipuleucel-T and a DNA vaccine. J Immunother Cancer 6(1):21. https://doi.org/10.1186/s40425-018-0333-y

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, Drijfhout JW, Wafelman AR, Oostendorp J, Fleuren GJ, Offringa R, van der Burg SH, Melief CJ (2008) 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. https://doi.org/10.1158/1078-0432.CCR-07-1881

    Article  CAS  PubMed  Google Scholar 

  26. Frazer IH, Quinn M, Nicklin JL, Tan J, Perrin LC, Ng P, O'Connor VM, White O, Wendt N, Martin J, Crowley JM, Edwards SJ, McKenzie AW, Mitchell SV, Maher DW, Pearse MJ, Basser RL (2004) Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX adjuvant in women with cervical intraepithelial neoplasia. Vaccine 23(2):172–181. https://doi.org/10.1016/j.vaccine.2004.05.013

    Article  CAS  PubMed  Google Scholar 

  27. Basu P, Mehta A, Jain M, Gupta S, Nagarkar RV, John S, Petit R (2018) A randomized phase 2 study of ADXS11-001 listeria monocytogenes-listeriolysin O immunotherapy with or without cisplatin in treatment of advanced cervical cancer. Int J Gynecol Cancer 28(4):764–772. https://doi.org/10.1097/IGC.0000000000001235

    Article  PubMed  PubMed Central  Google Scholar 

  28. Borysiewicz LK, Fiander A, Nimako M, Man S, Wilkinson GW, Westmoreland D, Evans AS, Adams M, Stacey SN, Boursnell ME, Rutherford E, Hickling JK, Inglis SC (1996) 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. https://doi.org/10.1016/s0140-6736(96)90674-1

    Article  CAS  PubMed  Google Scholar 

  29. Hung CF, Monie A, Alvarez RD, Wu TC (2007) DNA vaccines for cervical cancer: from bench to bedside. Exp Mol Med 39(6):679–689. https://doi.org/10.1038/emm.2007.74

    Article  CAS  PubMed  Google Scholar 

  30. Tyagi RK, Parmar R, Patel N (2017) A generic RNA pulsed DC based approach for developing therapeutic intervention against nasopharyngeal carcinoma. Hum Vaccin Immunother 13(4):854–866. https://doi.org/10.1080/21645515.2016.1256518

    Article  PubMed  Google Scholar 

  31. Liu W, Gao F, Zhao K, Zhao W, Fernando G, Thomas R, Frazer I (2002) Codon modified human papillomavirus type 16 E7 DNA vaccine enhances cytotoxic T-lymphocyte induction and anti-tumour activity. Virology 301(1):43–52. https://doi.org/10.1006/viro.2002.1584

    Article  CAS  PubMed  Google Scholar 

  32. Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C (2015) Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol 33(29):3235–3242. https://doi.org/10.1200/JCO.2015.61.6995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Leo PJ, Madeleine MM, Wang S, Schwartz SM, Newell F, Pettersson-Kymmer U, Hemminki K, Hallmans G, Tiews S, Steinberg W, Rader JS, Castro F, Safaeian M, Franco EL, Coutlee F, Ohlsson C, Cortes A, Marshall M, Mukhopadhyay P, Cremin K, Johnson LG, Trimble CL, Garland S, Tabrizi SN, Wentzensen N, Sitas F, Little J, Cruickshank M, Frazer IH, Hildesheim A, Brown MA (2017) Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study. PLoS Genet 13(8):e1006866. https://doi.org/10.1371/journal.pgen.1006866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Frazer IH, Chandra J (2019) Immunotherapy for HPV associated cancer. Papillomavirus Res 8:100176. https://doi.org/10.1016/j.pvr.2019.100176

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mattarollo SR, Rahimpour A, Choyce A, Godfrey DI, Leggatt GR, Frazer IH (2010) Invariant NKT cells in hyperplastic skin induce a local immune suppressive environment by IFN-gamma production. J Immunol 184(3):1242–1250

    Article  CAS  PubMed  Google Scholar 

  36. Zafereo ME, Hanasono MM, Rosenthal DI, Sturgis EM, Lewin JS, Roberts DB, Weber RS (2009) The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx. Cancer 115(24):5723–5733. https://doi.org/10.1002/cncr.24595

    Article  PubMed  Google Scholar 

  37. Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G, Jr Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D, Investigators K (2019) Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 394(10212):1915–1928. https://doi.org/10.1016/S0140-6736(19)32591-7

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank all patients participating in this study and complying with the protocol. We thank the Queensland Head and Neck Cancer Centre. We thank all relevant staff from the clinical trials unit of the Princess Alexandra Hospital who were involved in carrying out the clinical trial. We thank Clinical Network Services for compiling and analysing data. We thank the staff of TetraQ for the conduction of humoral immunology assays. We also thank Caroline Cooper from Pathology Queensland at the Princess Alexandra Hospital and staff of the Immunohistochemistry Laboratory, Tissue Pathology and Diagnostic Oncology at the Royal Prince Alfred Hospital in Camperdown, NSW, for conducting the RNAscope assay.

Funding

This study was funded by Admedus Vaccines Pty Ltd, Advance Queensland Ignite Ideas Fund and Jingang Medicine (Australia) Pty Ltd. Assay development and the vaccine technologies used in this study was in part supported by Queensland Government development grants, and by funding from the National Health and Medical Research Council of Australia.

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Author notes

  1. J. Chandra and W. P. Woo contributed equally.

Authors and Affiliations

  1. The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia

    J. Chandra, W. P. Woo, H. Y. Liu, R. Ladwa, Y. Xu, S. Hanson, B. Panizza, I. H. Frazer & Sandro V. Porceddu

  2. Princess Alexandra Hospital, Brisbane, QLD, Australia

    H. Y. Liu, M. McGrath, R. Ladwa, M. Brauer, B. Panizza & Sandro V. Porceddu

  3. Jingang Medicine (Australia) Pty Ltd, Brisbane, QLD, Australia

    W. P. Woo, N. Finlayson, Y. Xu & I. H. Frazer

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Contributions

SVP, IHF and NF conceptualised the study and acquired funding. SVP recruited patients and oversaw the delivery of the vaccine. SVP verified all clinical data entered onto the case research forms. HYL, MMcG, RL and BP were involved in identifying and recruiting patients to the trial. HYL and MMcG also provided assistance in clinical oversight during the delivery of the vaccine and entering of clinical data. WPW, MB, YX and SH were involved in data curation. JC, WPW and IHF formally analysed data. WPW, YX and SH performed experiments and collected data. WPW and YX developed and designed the methodology. WPW, MB, NF and SVP managed and coordinated trial execution. IHF, SVP and NF supervised the trial execution. JC prepared data visualisation and presentation. JC and WPW prepared the original draft of the manuscript. JC, WPW, IHF and SVP revised and edited the manuscript.

Corresponding author

Correspondence to Sandro V. Porceddu.

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Conflict of interest

We have read the journal’s policy and the authors of this manuscript have the following competing interests: WPW, YX and NF are employees of the company that funded the study. WPW, YX and NF hold share options. IHF is a board member of the company that funded the study, is a consultant to the company, is an inventor on the patent US 2011/0287039 A1, “Expression system for modulating an immune response” and WO 02/083181 A1, “Novel compositions and uses” which have been assigned to the company. IHF also holds share options in the company and is a minority shareholder (< 0.01% of the company shares). JC is a consultant to the company that funded the study. SVP reports personal fees from UpToDate, Merck, Celgene and Merck Sharpe & Dome. RL reports honoraria for speaking at symposia at Roche, Merck Serono and Ipsen, holds positions on advisory boards of Roche, Sanofi Aventis, Merck Sharpe & Dohme and Ipsen, and receives financial support for attending symposia and educational programmes at Ipsen and Novartis. We confirm that these commercial affiliations do not alter our adherence to the journals policies on sharing data and materials.

Ethical approval

This clinical trial was approved by the Metro South Hospital and Health Service Human Research Ethics Committee.

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Chandra, J., Woo, W.P., Finlayson, N. et al. A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC). Cancer Immunol Immunother 70, 743–753 (2021). https://doi.org/10.1007/s00262-020-02720-7

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