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Oncolytic HSV

Hiroshi Nakashima, Tran Nguyen, Kazue Kasai, Carmela Passaro, Hirotaka Ito, William F Goins, Imran Shaikh, Ronald Erdelyi, Reiko Nishihara, Ichiro Nakano, David A Reardon, Ana C Anderson, Vijay Kuchroo, E Antonio Chiocca
PURPOSE: Glioblastoma (GBM) is the most common primary central nervous system cancer in adults. Oncolytic HSV-1 (oHSV) is the first FDA-approved gene therapy approach for the treatment of malignant melanoma. For GBM, oHSVs need to be engineered to replicate within and be toxic to the glial tumor but not to normal brain parenchymal cells. We have thus engineered a novel oHSV to achieve these objectives. EXPERIMENTAL DESIGN: NG34 is an attenuated HSV-1 with deletions in the genes encoding viral ICP6 and ICP34...
March 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shinya Tada, Masakazu Hamada, Yoshiaki Yura
Oncolytic herpes simplex virus type 1 (HSV-1) strain RH2 induced immunogenic cell death (ICD) with the release and surface exposure of damage-associated molecular patterns (DAMPs) in squamous cell carcinoma (SCC) SCCVII cells. The supernatants of RH2-infected SCCVII cells also exhibited antitumor ability by intratumoral administration in SCCVII tumor-bearing mice. The supernatants of RH2-infected cells and mock-infected cells were concentrated to produce Med24 and MedC for proteomic analyses. In Med24, the up- and down-regulated proteins were observed...
January 23, 2018: Cancers
Wei Guo, Hao Song
Head and neck cancer represents the seventh most common cancer worldwide. Multidisciplinary sequential treatment was performed in patients with head and neck cancer. However, there is an urgent need for a new treatment approach that can effectively improve the outcomes of head and neck cancer patients with advanced stage. Gene therapy is a rapidly evolving field with head and neck cancer. It has been proved a promising way to improve the efficacy of antitumor treatment. China is at the forefront in clinical trials and practice of gene therapies in the world...
January 15, 2018: Human Gene Therapy
Weihua Lou, Fang Ji, Jianing Fu, Zhiqiang Han, Wen Di, Ning Zhang
INTRODUCTION: Oncolytic virotherapy has emerged as a novel frontier in the treatment of cancer. Among the viruses that entered clinical trials are the oncolytic herpes simplex virus-1 (HSV-1). Current oncolytic HSV-1 approved for clinical practice, and those in clinical trials are attenuated viruses, often deleted in the neurovirulence gene γ134.5, and in additional genes, which may result in a much more attenuated virus with reduced replication efficiency. Therefore, the transcriptional retargeting strategy by modifying the regulator elements flanking essential viral genes to achieve tumor-specific replication while maintaining as much of the viral genome has been representing alternative promising oncolytic virotherapy modality...
January 5, 2018: Journal of Cancer Research and Clinical Oncology
Richi Nakatake, Masaki Kaibori, Yusuke Nakamura, Yoshito Tanaka, Hideyuki Matushima, Tadayoshi Okumura, Takashi Murakami, Yasushi Ino, Tomoki Todo, Masanori Kon
Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. Oncolytic virus therapy is probably the next major breakthrough in cancer treatment. The third-generation oncolytic herpes simplex virus type 1 (HSV-1) T-01 kills tumor cells without damaging the surrounding normal tissues. Here we investigated the antitumor effects of T-01 on HCC and the host's immune response to HCC cells. The cytopathic activities of T-01 were tested in 14 human and one murine hepatoma cell lines in vitro...
December 30, 2017: Cancer Science
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ1 34.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
February 2018: Translational Oncology
Zahid M Delwar, Yvonne Kuo, Yan H Wen, Paul S Rennie, William Jia
The first oncolytic virotherapy employing HSV-1 (oHSV-1) was approved recently by the FDA to treat cancer, but further improvements in efficacy are needed to eradicate challenging refractory tumors such as glioblastomas (GBM). Microglia/macrophages comprising ~40% of a GBM tumor may limit virotherapeutic efficacy. Here we show these cells suppress oHSV-1 growth in gliomas by internalizing the virus through phagocytosis. Internalized virus remained capable of expressing reporter genes while viral replication was blocked...
November 8, 2017: Cancer Research
Eric K Ring, Rong Li, Blake P Moore, Li Nan, Virginia M Kelly, Xiaosi Han, Elizabeth A Beierle, James M Markert, Jianmei W Leavenworth, G Yancey Gillespie, Gregory K Friedman
Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45) and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1)...
December 15, 2017: Molecular Therapy Oncolytics
Y Furukawa, A Takasu, Y Yura
Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for oncolytic virotherapy. In squamous cell carcinoma (SCC) cells, the role of autophagy induced by neurovirulence gene-deficient HSV-1s in programmed cell death has not yet been elucidated. The oncolytic HSV-1 strain RH2, which lacks the γ34.5 gene and induces the fusion of human SCC cells, was used. RH2 replicated and induced cell death in SCC cells. RH2 infection was accompanied by the aggregation of microtubule-associated protein 1 light chain 3 (LC3) in the cytoplasm, the conversion of LC3-I to LC3-II and the formation of double-membrane vacuoles containing cell contents...
September 2017: Cancer Gene Therapy
Dipongkor Saha, Robert L Martuza, Samuel D Rabkin
No abstract text is available yet for this article.
July 2017: Oncoscience
Lauren M Oldfield, Peter Grzesik, Alexander A Voorhies, Nina Alperovich, Derek MacMath, Claudia D Najera, Diya Sabrina Chandra, Sanjana Prasad, Vladimir N Noskov, Michael G Montague, Robert M Friedman, Prashant J Desai, Sanjay Vashee
Here, we present a transformational approach to genome engineering of herpes simplex virus type 1 (HSV-1), which has a large DNA genome, using synthetic genomics tools. We believe this method will enable more rapid and complex modifications of HSV-1 and other large DNA viruses than previous technologies, facilitating many useful applications. Yeast transformation-associated recombination was used to clone 11 fragments comprising the HSV-1 strain KOS 152 kb genome. Using overlapping sequences between the adjacent pieces, we assembled the fragments into a complete virus genome in yeast, transferred it into an Escherichia coli host, and reconstituted infectious virus following transfection into mammalian cells...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
Rui Tanaka, Fumi Goshima, Shinichi Esaki, Yoshitaka Sato, Takayuki Murata, Yukihiro Nishiyama, Daisuke Watanabe, Hiroshi Kimura
Advanced melanoma has long been treated with chemotherapy using cytotoxic agents like dacarbazine (DTIC), but overall survival rates with these drugs have been generally low. Recently, immunoregulatory monoclonal antibodies and molecularly targeted therapy with a BRAF inhibitor and/or a MEK inhibitor, have been used to treat malignant melanoma and have improved the survival rate of patients with advanced melanoma. However, high prices of these drugs are problematic. In this study, we evaluated the oncolytic efficacy of HF10, an attenuated, replication-competent HSV, with DTIC in immunocompetent mice model of malignant melanoma...
2017: American Journal of Cancer Research
X J Liu, X Y Wang, J X Guo, H J Zhu, C R Zhang, Z H Ma
Objective: Constructed the recombinant HSV-1 deleted ICP47 and inserted human IL-12, and investigate the virus' replication ability and oncolytic property in vitro and vivo. Methods: The recombinant HSV-1 deleting ICP47 (MH1005) and then inserting human IL-12 (MH1006) were obtained with bacterial artificial chromosome technology.The replication ability and the efficiency of inhibiting tumor were detected in several nerve tumor cell lines infected with HSV-wt, MH1005 and MH1006 respectively.The murine tumor model was established by subcutaneous inoculation Neuro-2a cells on both sides of mice back respectively...
July 18, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Omid Hamid, Brianna Hoffner, Eduard Gasal, Jenny Hong, Richard D Carvajal
Oncolytic immunotherapy is a research area of cancer immunotherapy investigating the use of modified viruses to target cancer cells. A variety of different viral backbones (e.g., adenovirus, reovirus) with a diverse range of genetic modifications are currently being investigated for the treatment of a variety of cancers. The oncolytic virus that has advanced the furthest in clinical development is talimogene laherparepvec, a recombinant HSV-1 virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF)...
October 2017: Cancer Immunology, Immunotherapy: CII
Dhaval S Sanchala, Lokesh K Bhatt, Kedar S Prabhavalkar
Oncolytic viral therapy, which makes use of replication-competent lytic viruses, has emerged as a promising modality to treat malignancies. It has shown meaningful outcomes in both solid tumor and hematologic malignancies. Advancements during the last decade, mainly genetic engineering of oncolytic viruses have resulted in improved specificity and efficacy of oncolytic viruses in cancer therapeutics. Oncolytic viral therapy for treating cancer with herpes simplex virus-1 has been of particular interest owing to its range of benefits like: (a) large genome and power to infiltrate in the tumor, (b) easy access to manipulation with the flexibility to insert multiple transgenes, (c) infecting majority of the malignant cell types with quick replication in the infected cells and (d) as Anti-HSV agent to terminate HSV replication...
2017: Frontiers in Pharmacology
Shahriyar Abdoli, Farzin Roohvand, Ladan Teimoori-Toolabi, Mohammad Ali Shokrgozar, Mina Bahrololoumi, Kayhan Azadmanesh
Background: Oncolytic herpes simplex virus (oHSV)-based vectors lacking γ34.5 gene, are considered as ideal templates to construct efficient vectors for (targeted) cancer gene therapy. Herein, we reported the construction of three single/dually-flourescence labeled and γ34.5-deleted, recombinant HSV-1 vectors for rapid generation and easy selection/isolation of different HSV-Based vectors. Methods: Generation of recombinant viruses was performed with conventional homologous recombination methods using green fluorescent protein (GFP) and BleCherry harboring shuttle vectors...
July 2017: Iranian Biomedical Journal
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose : Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
Keri A Streby, James I Geller, Mark A Currier, Patrick S Warren, John M Racadio, Alexander J Towbin, Michele R Vaughan, Melinda Triplet, Kristy Ott-Napier, Devon J Dishman, Lori R Backus, Beth Stockman, Marianne Brunner, Kathleen Simpson, Robert Spavin, Joe Conner, Timothy P Cripe
Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric patients with cancer, we conducted a phase I trial of image-guided injection in young patients with relapsed or refractory extracranial cancers.Experimental Design: We delivered a single dose of 10(5) to 10(7) infectious units of HSV1716 via computed tomography-guided intratumoral injection and measured tumor responses by imaging...
May 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yoshiaki Yura
A virus is a pathogenic organism that causes a number of infectious diseases in humans. The oral cavity is the site at which viruses enter and are excreted from the human body. Herpes simplex virus type 1 (HSV-1) produces the primary infectious disease, gingivostomatitis, and recurrent disease, labial herpes. HSV-1 is one of the most extensively investigated viruses used for cancer therapy. In principle, HSV-1 infects epithelial cells and neuronal cells and exhibits cytotoxicity due to its cytopathic effects on these cells...
May 2017: Japanese Dental Science Review
Biljana Petrovic, Tatiana Gianni, Valentina Gatta, Gabriella Campadelli-Fiume
Herpes simplex virus (HSV) entry into the cells requires glycoproteins gD, gH/gL and gB, activated in a cascade fashion by conformational modifications induced by cognate receptors and intermolecular signaling. The receptors are nectin1 and HVEM (Herpes virus entry mediator) for gD, and αvβ6 or αvβ8 integrin for gH. In earlier work, insertion of a single chain antibody (scFv) to the cancer receptor HER2 (human epidermal growth factor receptor 2) in gD, or in gH, resulted in HSVs specifically retargeted to the HER2-positive cancer cells, hence in highly specific non-attenuated oncolytic agents...
April 2017: PLoS Pathogens
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