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).
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).
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.
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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Enzyme-linked immunosorbent assay
Enzyme-linked immunosorbent spot
Head and neck cancer
Oropharyngeal squamous cell carcinoma
Peripheral blood mononuclear cells
Treatment emergent adverse events
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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.
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.
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.
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
- Human papillomavirus
- Head and neck cancer
- Oropharyngeal squamous cell carcinoma
- DNA vaccine
- HPV E6 and E7 oncoproteins