Preclinical Development of Oncolytic Immunovirotherapy for Treatment of HPVPOS Cancers

Molecular Therapy Oncolytics
Lukkana SuksanpaisanRosa Maria Diaz

Abstract

Immunotherapy for HPVPOS malignancies is attractive because well-defined, viral, non-self tumor antigens exist as targets. Several approaches to vaccinate therapeutically against HPV E6 and E7 antigens have been adopted, including viral platforms such as VSV. A major advantage of VSV expressing these antigens is that VSV also acts as an oncolytic virus, leading to direct tumor cell killing and induction of effective anti-E6 and anti-E7 T cell responses. We have also shown that addition of immune adjuvant genes, such as IFNβ, further enhances safety and/or efficacy of VSV-based oncolytic immunovirotherapies. However, multiple designs of the viral vector are possible-with respect to levels of immunogen expression and method of virus attenuation-and optimal designs have not previously been tested head-to-head. Here, we tested three different VSV engineered to express a non-oncogenic HPV16 E7/6 fusion protein for their immunotherapeutic and oncolytic properties. We assessed their profiles of efficacy and toxicity against HPVPOS and HPVNEG murine tumor models and determined the optimal route of administration. Our data show that VSV is an excellent platform for the oncolytic immunovirotherapy of tumors expressing HPV target antigens...Continue Reading

Citations

Jul 20, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Luke RussellRosa Maria Diaz
Jun 3, 2021·Viruses·Nathália Alves Araújo de AlmeidaVanessa Salete de Paula

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Datasets Mentioned

BETA
K02718

Methods Mentioned

BETA
flow cytometry
Assay
PCR
transgenic
density gradient centrifugation

Clinical Trials Mentioned

NCT02285816
NCT02879760

Software Mentioned

GraphPad Prism
FlowJo
TreeStar

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