A Phase 1 Trial Assessing the Safety and Tolerability of a Therapeutic DNA Vaccination Against HPV16 and HPV18 E6/E7 Oncogenes After Chemoradiation for Cervical Cancer

Int J Radiat Oncol Biol Phys. 2020 Jul 1;107(3):487-498. doi: 10.1016/j.ijrobp.2020.02.031. Epub 2020 Mar 7.


Purpose: This study assessed the safety and tolerability of therapeutic immunization against the human papillomavirus (HPV) viral oncoproteins E6 and E7 in patients with cervical cancer after chemoradiation.

Methods and materials: MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks. The primary endpoints were incidence of adverse events and injection site reactions. Immune responses against HPV antigens were measured by ELISpot for interferon-γ (IFNγ), enzyme-linked immunosorbent assay for antibody responses and multiplexed immunofluorescence for immune cells in cervical biopsy specimens.

Results: Ten patients (cohort 1, n = 7; cohort 2, n = 3) with HPV16 (n = 7) or HPV18 (n = 3) cervical cancers received MEDI0457 after chemoradiation. Treatment-related adverse events were all grade 1, primarily related to the injection site. Eight of 10 patients had detectable cellular or humoral immune responses against HPV antigens after chemoradiation and vaccination: 6 of 10 patients generated anti-HPV antibody responses and 6 of 10 patients generated IFNγ-producing T cell responses. At the completion of chemoradiation and vaccination, cervical biopsy specimens had detectable CD8+ T cells and decreased PD-1+CD8+, PD-L1+CD8+, and PD-L1+CD68+ subpopulations. All patients cleared detectable HPV DNA in cervical biopsies by completion of chemoradiation and vaccination.

Conclusions: Adjuvant MEDI0457 is safe and well tolerated after chemoradiation for locally advanced or recurrent cervical cancers, supporting further investigation into combining tumor-specific vaccines with radiation therapy.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chemoradiotherapy*
  • DNA-Binding Proteins / immunology
  • Female
  • Human papillomavirus 16 / drug effects
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 16 / physiology
  • Human papillomavirus 16 / radiation effects
  • Human papillomavirus 18 / drug effects
  • Human papillomavirus 18 / immunology*
  • Human papillomavirus 18 / physiology
  • Human papillomavirus 18 / radiation effects
  • Humans
  • Middle Aged
  • Oncogene Proteins, Viral / immunology
  • Papillomavirus E7 Proteins / immunology
  • Repressor Proteins / immunology
  • Safety*
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / therapy*
  • Uterine Cervical Neoplasms / virology*
  • Vaccines, DNA / adverse effects*


  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • E7 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • Vaccines, DNA
  • oncogene protein E7, Human papillomavirus type 16