VIRUS PRODUCTION CORE The primary objective of the Virus Production Core (VPC) is to continue to provide highly purified, high titer virus stocks, in support of studies outlined in each of the Projects and in the EGAM Core within this Program. Establishment of such stocks is essential to ensure consistency and reproducibility between experiments and laboratories for all of the Projects within this Program. Each lot is regularly tested for titer stability, foreign gene expression, and genotype stability. Additional functions of the VPC have included the following: (I) regular update of the Master Virus database as new viruses are produced, (ll) development of virus-specific standard operating protocols (SOPs) to achieve highest titers, and (III) maintenance of the Program website to report recent developments, including list of publications and upcoming meetings. However, translation of our novel vectors into the clinical setting has tjeen critically hampered by the inability to produce the vectors locally using Good Laboratory Practice (GLP) and current Good Manufacturing Practices (cGMP). Without this capability, production of novel vectors, like our IL-12 expressing candidate virus, M032, for the safety and toxicity studies required for investigational new drug (IND) applications and for the performance eariy stage clinical trials, had to be outsourced. Recently, to address this critical problem, the Comprehensive Cancer Center at UAB provided funds to renovate the existing Vaccine and Vector Production Facility (WPF) within the Special Building for Cancer Research to acquire the capability to produce GLP-quality therapeutic vectors. Additional financial support through the UAB Health Services Foundation General Endowment Fund was obtained in March, 2008. Thus, to accelerate the translation of novel vectors into the preclinical arena, additional objectives of the VPC are being incorporated into this renewal application. These include: (/) the adaptation of existing standard operating protocols (SOPs) for HSV production and the development of new SOPs that are specific for the WPF and our oncolytic HSV vectors, (If) the production of Master Cell Bank stocks of qualified Vero cells for the production of GLP-quality Working Cell Banks and Master Virus Stocks, (///) the completion of a series of certification tests to generate a certificate of analysis for each lot of virus prior to distribution to their respective Projects, or to the EGAM Core (Core B- Gillespie). The final objective of the VPC will be to produce and qualify the new cell line to be developed in Project 1.

Public Health Relevance

A Core facility for the production of highly purified, high titer virus stocks is essential to ensure consistency and reproducibility between experiments and laboratories, both In vitro and In vivo, for all of the Projects within this Program. Additionally, achieving the capability to translate our novel vectors into the clinical setting requires the use of Good Laboratory Practice (GLP) and current Good Manufacturing Practices (cGMP), as specified by the Food and Drug Administration (FDA). Local production of novel vectors, like our IL-12 expressing candidate virus, M032, would expedite the safety and toxicity studies that are required for submission of investigational new drug (IND) applications and to perform early stage clinical trials.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-GRB-S)
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University of Alabama Birmingham
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Foreman, Paul M; Friedman, Gregory K; Cassady, Kevin A et al. (2017) Oncolytic Virotherapy for the Treatment of Malignant Glioma. Neurotherapeutics 14:333-344
Ring, Eric K; Markert, James M; Gillespie, G Yancey et al. (2017) Checkpoint Proteins in Pediatric Brain and Extracranial Solid Tumors: Opportunities for Immunotherapy. Clin Cancer Res 23:342-350
Ring, Eric K; Li, Rong; Moore, Blake P et al. (2017) Newly Characterized Murine Undifferentiated Sarcoma Models Sensitive to Virotherapy with Oncolytic HSV-1 M002. Mol Ther Oncolytics 7:27-36
Friedman, Gregory K; Moore, Blake P; Nan, Li et al. (2016) Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses. Neuro Oncol 18:227-35
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Dobbins, G Clement; Ugai, Hideyo; Curiel, David T et al. (2015) A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents. PLoS One 10:e0145272
Shu, Minfeng; Du, Te; Zhou, Grace et al. (2015) Role of activating transcription factor 3 in the synthesis of latency-associated transcript and maintenance of herpes simplex virus 1 in latent state in ganglia. Proc Natl Acad Sci U S A 112:E5420-6
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