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)

• Published in: Cancer Immunology, Immunotherapy Vol. 70; no. 3; pp. 743 - 753
• Main Authors: Chandra, J., Woo, W. P., Finlayson, N., Liu, H. Y., McGrath, M., Ladwa, R., Brauer, M., Xu, Y., Hanson, S., Panizza, B., Frazer, I. H., Porceddu, Sandro V.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2021; Springer Nature B.V
• Subjects: Adverse events; Alphapapillomavirus - immunology; Antibodies, Viral - immunology; Antigens; Cancer Research; Deoxyribonucleic acid; DNA; DNA vaccines; Dosage; Enzyme-linked immunosorbent assay; Enzymes; Female; Head & neck cancer; Head and Neck Neoplasms - diagnosis; Head and Neck Neoplasms - etiology; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - prevention & control; Human papillomavirus; Humans; Immunity, Cellular - immunology; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulin G - immunology; Immunology; Injection; Lymphocytes T; Male; Medicine; Medicine & Public Health; Metastases; Oncology; Original; Original Article; Papillomavirus Infections - complications; Papillomavirus Infections - immunology; Papillomavirus Infections - prevention & control; Papillomavirus Infections - virology; Papillomavirus Vaccines - administration & dosage; Papillomavirus Vaccines - adverse effects; Papillomavirus Vaccines - immunology; Squamous cell carcinoma; Throat cancer; Treatment Outcome; Tumors; Vaccination; Vaccines; Vaccines, DNA - immunology; γ-Interferon; DNA vaccine; Oropharyngeal squamous cell carcinoma; Head and neck cancer; Human papillomavirus; HPV E6 and E7 oncoproteins; Immunotherapy
• ISSN: 0340-7004; 1432-0851; 1432-0851
• DOI: 10.1007/s00262-020-02720-7

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.