Molecular Therapy: Oncolytics (Jan 2016)

Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100

  • Matthew P Morrow,
  • Kimberly A Kraynyak,
  • Albert J Sylvester,
  • Xuefei Shen,
  • Dinah Amante,
  • Lindsay Sakata,
  • Lamar Parker,
  • Jian Yan,
  • Jean Boyer,
  • Christian Roh,
  • Laurent Humeau,
  • Amir S Khan,
  • Kate Broderick,
  • Kathleen Marcozzi-Pierce,
  • Mary Giffear,
  • Jessica Lee,
  • Cornelia L Trimble,
  • J Joseph Kim,
  • Niranjan Y Sardesai,
  • David B Weiner,
  • Mark L Bagarazzi

DOI
https://doi.org/10.1038/mto.2016.25
Journal volume & issue
Vol. 3, no. C

Abstract

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We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV)16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFN)γ production, tumor necrosis factor (TNF)α production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR) sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth “booster” dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100.