TY - JOUR
T1 - Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100
AU - Morrow, Matthew P.
AU - Kraynyak, Kimberly A.
AU - Sylvester, Albert J.
AU - Shen, Xuefei
AU - Amante, Dinah
AU - Sakata, Lindsay
AU - Parker, Lamar
AU - Yan, Jian
AU - Boyer, Jean
AU - Roh, Christian
AU - Humeau, Laurent
AU - Khan, Amir S.
AU - Broderick, Kate
AU - Marcozzi-Pierce, Kathleen
AU - Giffear, Mary
AU - Lee, Jessica
AU - Trimble, Cornelia L.
AU - Kim, J. Joseph
AU - Sardesai, Niranjan Y.
AU - Weiner, David B.
AU - Bagarazzi, Mark L.
N1 - Publisher Copyright:
© 2016 The Author (S).
PY - 2016/11/30
Y1 - 2016/11/30
N2 - 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.
AB - 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.
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U2 - 10.1038/mto.2016.25
DO - 10.1038/mto.2016.25
M3 - Article
C2 - 28054033
AN - SCOPUS:84999648267
SN - 2372-7705
VL - 3
SP - 16025
JO - Molecular Therapy Oncolytics
JF - Molecular Therapy Oncolytics
M1 - 16025
ER -