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Oncolytic HSV

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https://www.readbyqxmd.com/read/28176649/oncolytic-herpes-simplex-virus-vectors-fully-retargeted-to-tumor-associated-antigens
#1
Hiroaki Uchida, Hirofumi Hamada, Kenji Nakano, Heechung Kwon, Hideaki Tahara, Justus B Cohen, Joseph C Glorioso
Oncolytic virotherapy is a novel therapeutic modality for malignant diseases that exploits selective viral replication in cancer cells. Herpes simplex virus (HSV) is a promising agent for oncolytic virotherapy due to its broad cell tropism and the identification of mutations that favor its replication in tumor over normal cells. However, these attenuating mutations also tend to limit the potency of current oncolytic HSV vectors that have entered clinical studies. As an alternative, vector retargeting to novel entry receptors has the potential to achieve tumor specificity at the stage of virus entry, eliminating the need for replication-attenuating mutations...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28147331/aurora-a-kinase-inhibition-enhances-oncolytic-herpes-virotherapy-through-cytotoxic-synergy-and-innate-cellular-immune-modulation
#2
Mark A Currier, Les Sprague, Tilat A Rizvi, Brooke Nartker, Chun-Yu Chen, Pin-Yi Wang, Brian J Hutzen, Meghan R Franczek, Ami V Patel, Katherine E Chaney, Keri A Streby, Jeffrey A Ecsedy, Joe Conner, Nancy Ratner, Timothy P Cripe
Malignant peripheral nerve sheath tumor (MPNST) and neuroblastoma models respond to the investigational small molecule Aurora A kinase inhibitor, alisertib. We previously reported that MPNST and neuroblastomas are also susceptible to oncolytic herpes virus (oHSV) therapy. Herein, we show that combination of alisertib and HSV1716(HSV1716), a virus derived from HSV-1 and attenuated by deletion of RL1, exhibits significantly increased antitumor efficacy compared to either monotherapy. Alisertib and HSV1716 reduced tumor growth and increased survival in two xenograft models of MPNST and neuroblastoma...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28093274/a-direct-quantitative-pcr-based-measurement-of-herpes-simplex-virus-susceptibility-to-antiviral-drugs-and-neutralizing-antibodies
#3
Dezső P Virók, Ildikó Eszik, Tímea Mosolygó, Kamil Önder, Valéria Endrész, Katalin Burián
Herpes simplex viruses (HSV) are common human pathogens that can cause painful but benign manifestations and recurrent complaints, but can also cause significant morbidity and mortality on infection of the eye or brain and with disseminated infection of an immunosuppressed patient or a neonate. HSV growth inhibition measurement by plaque or yield reduction is a key task in the development of novel antiviral compounds but the manual methods are very labour intensive. The sensitive and specific PCR technology could be an effective method for quantitation of HSV DNA related to virus replication; however the currently described PCR approaches have a major limitation, namely the requirement of purification of DNA from the infected cells...
April 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28087981/humanized-chondroitinase-abc-sensitizes-glioblastoma-cells-to-temozolomide
#4
Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard-Blessing, Jeffrey Wojton, Balveen Kaur
INTRODUCTION: Malignant gliomas (GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extra cellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM...
January 14, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28074746/oncology-s-trojan-horse-using-viruses-to-battle-cancer
#5
Heena J Mavani, Jeannette Y Wick
: In 2016, the American health care system was faced with more than 1.6 million new cases of cancer, and individuals older than 65 years of age will be affected disproportionately. Many older individuals are poor candidates for traditional treatments (e.g., chemotherapy, radiation) because of actual or potential treatment-related adverse events. Researchers continuously look for novel therapeutic strategies, and an exciting new one is on the horizon: virotherapy. Viruses' ability to infect and kill human cells makes them promising cancer treatments...
December 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28061981/talimogene-laherparepvec-t-vec-for-the-treatment-of-melanoma-and-other-cancers
#6
REVIEW
Claud Grigg, Zoë Blake, Robyn Gartrell, Adrian Sacher, Bret Taback, Yvonne Saenger
Talimogene laherparepvec (T-Vec) is the first live virus to be approved by the US Food and Drug Administration for the treatment of cancer. This engineered version of herpes simplex virus type 1 (HSV-1) is the product of decades of preclinical work aimed at identifying and modifying aspects of the viral genome involved in virulence and immunogenicity. T-Vec preferentially infects and lyses tumor cells and, in some cases, induces a systemic immune response against the tumor. These properties have translated into significant and durable clinical responses, particularly in advanced melanoma...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27867771/prospect-and-progress-of-oncolytic-viruses-for-treating-peripheral-nerve-sheath-tumors
#7
Slawomir Antoszczyk, Samuel D Rabkin
INTRODUCTION: Peripheral nerve sheath tumors (PNSTs) are an assorted group of neoplasms originating from neuroectoderm and growing in peripheral nerves. Malignant transformation leads to a poor prognosis and is often lethal. Current treatment of PNSTs is predominantly surgical, which is often incomplete or accompanied by significant loss of function, in conjunction with radiotherapy and/or chemotherapy, for which the benefits are inconclusive. Oncolytic viruses (OVs) efficiently kill tumor cells while remaining safe for normal tissues, and are a novel antitumor therapy for patients with PNSTs...
2016: Expert Opinion on Orphan Drugs
https://www.readbyqxmd.com/read/27852701/bai1-orchestrates-macrophage-inflammatory-response-to-hsv-infection-implications-for-oncolytic-viral-therapy
#8
Chelsea Bolyard, W Hans Meisen, Yeshavanth Banasavadi-Siddegowda, Jayson Hardcastle, Ji Young Yoo, Eric S Wohleb, Jeffrey Wojton, Jun-Ge Yu, Samuel Dubin, Maninder Khosla, Bo Xu, Jonathan Smith, Christopher Alvarez-Breckenridge, Pete Pow-Anpongkul, Flavia Pichiorri, Jianying Zhang, Matthew Old, Dan Zhu, Erwin G Van Meir, Jonathan P Godbout, Michael A Caligiuri, Jianhua Yu, Balveen Kaur
PURPOSE: Brain angiogenesis inhibitor (BAI1) facilitates phagocytosis and bacterial pathogen clearance by macrophages; however, its role in viral infections is unknown. Here, we examined the role of BAI1, and its N-terminal cleavage fragment (Vstat120) in antiviral macrophage responses to oncolytic herpes simplex virus (oHSV). EXPERIMENTAL DESIGN: Changes in infiltration and activation of monocytic and microglial cells after treatment of glioma-bearing mice brains with a control (rHSVQ1) or Vstat120-expressing (RAMBO) oHSV was analyzed using flow cytometry...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27751346/effect-of-repeat-dosing-of-engineered-oncolytic-herpes-simplex-virus-on-preclinical-models-of-rhabdomyosarcoma
#9
Alicia M Waters, Laura L Stafman, Evan F Garner, Smitha Mruthyunjayappa, Jerry E Stewart, Gregory K Friedman, Jennifer M Coleman, James M Markert, G Yancey Gillespie, Elizabeth A Beierle
Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ134...
October 2016: Translational Oncology
https://www.readbyqxmd.com/read/27713537/increasing-the-efficiency-of-crispr-cas9-mediated-precise-genome-editing-of-hsv-1-virus-in-human-cells
#10
Chaolong Lin, Huanhuan Li, Mengru Hao, Dan Xiong, Yong Luo, Chenghao Huang, Quan Yuan, Jun Zhang, Ningshao Xia
Genetically modified HSV-1 viruses serve as promising vectors for tumour therapy and vaccine development. The CRISPR/Cas9 system is one of the most powerful tools for precise gene editing of the genomes of organisms. However, whether the CRISPR/Cas9 system can precisely and efficiently make gene replacements in the genome of HSV-1 remains essentially unknown. Here, we reported CRISPR/Cas9-mediated editing of the HSV-1 genome in human cells, including the knockout and replacement of large genes. In established cells stably expressing CRISPR/Cas9, gRNA in coordination with Cas9 could direct a precise cleavage within a pre-defined target region, and foreign genes were successfully used to replace the target gene seamlessly by HDR-mediated gene replacement...
October 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27707922/syncytial-mutations-do-not-impair-the-specificity-of-entry-and-spread-of-a-glycoprotein-d-receptor-retargeted-herpes-simplex-virus
#11
Yu Okubo, Hiroaki Uchida, Aika Wakata, Takuma Suzuki, Tomoko Shibata, Hitomi Ikeda, Miki Yamaguchi, Justus B Cohen, Joseph C Glorioso, Mitsuo Tagaya, Hirofumi Hamada, Hideaki Tahara
: Membrane fusion, which is the key process for both initial cell entry and subsequent lateral spread of herpes simplex virus (HSV), requires the four envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause multinucleated giant cells, termed syncytia. Here we asked whether interaction of gD with a cognate entry receptor remains indispensable for initiating membrane fusion of syncytial strains...
December 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27610392/effect-of-hsv-il12-loaded-tumor-cell-based-vaccination-in-a-mouse-model-of-high-grade-neuroblastoma
#12
David F Bauer, Larisa Pereboeva, G Yancey Gillespie, Gretchen A Cloud, Osama Elzafarany, Catherine Langford, James M Markert, Lawrence S Lamb
We designed multimodal tumor vaccine that consists of irradiated tumor cells infected with the oncolytic IL-12-expressing HSV-1 virus, M002. This vaccine was tested against the syngeneic neuroblastoma mouse model Neuro 2a injected into the right caudate nucleus of the immunocompetent A/J mice. Mice were vaccinated via intramuscular injection of multimodal vaccine or uninfected irradiated tumor cells at seven and 14 days after tumor establishment. While there was no survival difference between groups vaccinated with cell-based vaccine applied following tumor injection, a premunition prime/boost vaccination strategy produced a significant survival advantage in both groups and sustained immune response to an intracranial rechallenge of the same tumor...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27497296/oncolytic-herpes-simplex-virus-interactions-with-the-host-immune-system
#13
REVIEW
Dipongkor Saha, Hiroaki Wakimoto, Samuel D Rabkin
Oncolytic viruses (OVs), like oncolytic herpes simplex virus (oHSV), are genetically engineered to selectively replicate in and kill cancer cells, while sparing normal cells. Initial OV infection, cell death, and subsequent OV propagation within the tumor microenvironment leads to a cascade of host responses (innate and adaptive), reflective of natural anti-viral immune responses. These host-virus interactions are critical to the balance between OV activities, anti-viral immune responses limiting OV, and induction of anti-tumor immunity...
December 2016: Current Opinion in Virology
https://www.readbyqxmd.com/read/27486853/oncolytic-virus-therapy-a-new-era-of-cancer-treatment-at-dawn
#14
REVIEW
Hiroshi Fukuhara, Yasushi Ino, Tomoki Todo
Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe...
October 2016: Cancer Science
https://www.readbyqxmd.com/read/27446014/liposome-mediated-herpes-simplex-virus-uptake-is-glycoprotein-d-receptor-independent-but-requires-heparan-sulfate
#15
Lorrie A Burnham, Dinesh Jaishankar, Jeffrey M Thompson, Kevin S Jones, Deepak Shukla, Vaibhav Tiwari
Cationic liposomes are widely used to facilitate introduction of genetic material into target cells during transfection. This study describes a non-receptor mediated herpes simplex virus type-1 (HSV-1) entry into the Chinese hamster ovary (CHO-K1) cells that naturally lack glycoprotein D (gD)-receptors using a commercially available cationic liposome: lipofectamine. Presence of cell surface heparan sulfate (HS) increased the levels of viral entry indicating a potential role of HS in this mode of entry. Loss of viral entry in the presence of actin de-polymerizing or lysosomotropic agents suggests that this mode of entry results in the endocytosis of the lipofectamine-virus mixture...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27390350/bortezomib-treatment-sensitizes-oncolytic-hsv-1-treated-tumors-to-nk-cell-immunotherapy
#16
Ji Young Yoo, Alena Cristina Jaime-Ramirez, Chelsea Bolyard, Hongsheng Dai, Tejaswini Nallanagulagari, Jeffrey Wojton, Brian S Hurwitz, Theresa Relation, Tae Jin Lee, Michael T Lotze, Jun-Ge Yu, Jianying Zhang, Carlo M Croce, Jianhua Yu, Michael A Caligiuri, Matthew Old, Balveen Kaur
PURPOSE: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy. EXPERIMENTAL DESIGN: Western blot, flow cytometry, and caspase 3/7 activity assays were used to evaluate the induction of apoptosis/autophagy and/or necroptotic cell death...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27347556/oncolytic-herpes-simplex-virus-kills-stem-like-tumor-initiating-colon-cancer-cells
#17
Susanne G Warner, Dana Haddad, Joyce Au, Joshua S Carson, Michael P O'Leary, Christina Lewis, Sebastien Monette, Yuman Fong
Stem-like tumor-initiating cells (TICs) are implicated in cancer progression and recurrence, and can be identified by sphere-formation and tumorigenicity assays. Oncolytic viruses infect, replicate in, and kill a variety of cancer cells. In this study, we seek proof of principle that TICs are susceptible to viral infection. HCT8 human colon cancer cells were subjected to serum-free culture to generate TIC tumorspheres. Parent cells and TICs were infected with HSV-1 subtype NV1066. Cytotoxicity, viral replication, and Akt1 expression were assessed...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27344736/-oncolytic-virus-therapy-using-recombinant-hsv-1-for-prostate-cancer
#18
Shigenori Kakutani, Hiroshi Fukuhara, Yukio Homma
No abstract text is available yet for this article.
May 20, 2016: Nihon Rinsho. Japanese Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27322463/human-trial-of-a-genetically-modified-herpes-simplex-virus-for-rapid-detection-of-positive-peritoneal-cytology-in-the-staging-of-pancreatic-cancer
#19
Kaitlyn J Kelly, Joyce Wong, Mithat Gönen, Peter Allen, Murray Brennan, Daniel Coit, Yuman Fong
INTRODUCTION: Patients with peritoneal dissemination of pancreatic adenocarcinoma do not benefit from surgical resection, but radiologic and cytologic detection of peritoneal cancer lack sensitivity. This trial sought to determine if an oncolytic virus may be used as a diagnostic agent to detect peritoneal cancer. METHODS: Peritoneal washings from patients with pancreatic adenocarcinoma were incubated with the enhanced green fluorescent protein (eGFP)-expressing oncolytic herpes simplex virus (HSV) NV1066...
May 2016: EBioMedicine
https://www.readbyqxmd.com/read/27314913/design-of-a-phase-i-clinical-trial-to-evaluate-m032-a-genetically-engineered-hsv-1-expressing-il-12-in-patients-with-recurrent-progressive-glioblastoma-multiforme-anaplastic-astrocytoma-or-gliosarcoma
#20
Daxa M Patel, Paul M Foreman, L Burt Nabors, Kristen O Riley, G Yancey Gillespie, James M Markert
M032 is a second-generation oncolytic herpes simplex virus (oHSV) that selectively replicates in tumor cells. M032 kills tumor cells directly through oncolytic replication and then proceeds to infect tumor cells in proximity, continuing the process of tumor destruction. In addition to this direct oncolytic activity, the virus carries a therapeutic payload-thus acting as a gene therapy vector-and causes the tumor cell to synthesize and secrete the immunity-stimulating protein interleukin-12 (IL-12) before cell death...
June 2016: Human Gene Therapy. Clinical Development
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