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

By 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 and Mark L Bagarazzi

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)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

Topics: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Publisher: Elsevier
Year: 2016
DOI identifier: 10.1038/mto.2016.25
OAI identifier: oai:doaj.org/article:6cdec84404f44e6da5cce111757a5347
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