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. WeinerMark L. Bagarazzi

Research output: Contribution to journalArticlepeer-review

Abstract

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) 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.

Original languageEnglish (US)
Article number16025
Pages (from-to)16025
Number of pages1
JournalMolecular Therapy - Oncolytics
Volume3
DOIs
StatePublished - Nov 30 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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