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Oncolytic viruses

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https://www.readbyqxmd.com/read/28529900/immunotherapy-and-radiation-therapy-for-operable-early-stage-and-locally-advanced-non-small-cell-lung-cancer
#1
REVIEW
Neil K Taunk, Andreas Rimner, Melissa Culligan, Joseph S Friedberg, Julie Brahmer, Jamie Chaft
Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality. Although a significant proportion of patients can be cured with surgery, with or without adjuvant or neoadjuvant chemotherapy and radiation, a significant proportion of patients will fail, particularly distantly. Over fifty percent of patients present with stage IV disease. There are multiple forms of immunotherapy available including T-cell transfer, cytokine therapy, and oncolytic viruses. Checkpoint inhibitors have shown tremendous activity in NSCLC and are currently under intense study given promising data on response...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28527723/activation-of-nrf2-signaling-augments-vesicular-stomatitis-virus-oncolysis-via-autophagy-driven-suppression-of-antiviral-immunity
#2
David Olagnier, Rassin R Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V Knatko, Albena T Dinkova-Kostova, John Hiscott, Rongtuan Lin
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28525954/construction-of-various-%C3%AE-34-5-deleted-fluorescent-expressing-oncolytic-herpes-simplex-type-1-ohsv-for-generation-and-isolation-of-hsv-based-vectors
#3
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
https://www.readbyqxmd.com/read/28514874/oncolytic-recombinant-vesicular-stomatitis-virus-vsv-is-nonpathogenic-and-non-transmissible-in-pigs-a-natural-host-of-vsv
#4
Lauro Velazquez-Salinas, Shruthi Naik, Steven Pauszek, Kah-Whye Peng, Stephen J Russell, Luis Rodriguez
Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus that naturally causes disease in livestock including horses, cattle and pigs. The two main identified VSV strains are the New Jersey (VSNJV) and Indiana (VSIV) strains. VSV is a rapidly replicating, potently immunogenic virus that has been engineered to develop novel oncolytic therapies for cancer treatment. Swine are a natural host for VSV and provide a relevant and well-established model, amenable to biological sampling to monitor virus shedding and neutralizing antibodies...
May 17, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28512387/oncolytic-virus-based-immunotherapies-for-hepatocellular-carcinoma
#5
REVIEW
So Young Yoo, Narayanasamy Badrinath, Hyun Young Woo, Jeong Heo
Hepatocellular carcinoma is highly refractory cancer which is resistant to conventional chemotherapy and radiotherapy, carrying a dismal prognosis. Although many anticancer drugs have been developed for treating HCC, sorafenib is the only effective treatment, but it only prolongs survival duration for about 3 months. Recently, oncolytic virotherapy has shown promising results in treating HCCs and the effects can be more enhanced by adopting immune modulatory molecules. This review discusses the current status of treating HCC and the effective strategy of oncolytic virus-based immunotherapy for the treatment of HCCs...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28507792/oncolytic-measles-virus-encoding-interleukin-12-mediates-potent-antitumor-effects-through-t-cell-activation
#6
Rūta Veinalde, Christian Grossardt, Laura Hartmann, Marie-Claude Bourgeois-Daigneault, John C Bell, Dirk Jäger, Christof von Kalle, Guy Ungerechts, Christine E Engeland
Combination of oncolytic virotherapy with immunomodulators is emerging as a promising therapeutic strategy for numerous tumor entities. In this study, we developed measles Schwarz vaccine strain vectors encoding immunomodulators to support different phases in the establishment of antitumor immune responses. Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein (MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively, as the most effective...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#7
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
https://www.readbyqxmd.com/read/28496337/immunogenicity-of-oncolytic-vaccinia-viruses-jx-gfp-and-tg6002-in-a-human-melanoma-in-vitro-model-studying-immunogenic-cell-death-dendritic-cell-maturation-and-interaction-with-cytotoxic-t-lymphocytes
#8
B Heinrich, J Klein, M Delic, K Goepfert, V Engel, L Geberzahn, M Lusky, P Erbs, X Preville, M Moehler
Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28495911/intratumoral-injection-of-hsv1716-an-oncolytic-herpes-virus-is-safe-and-shows-evidence-of-immune-response-and-viral-replication-in-young-cancer-patients
#9
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
https://www.readbyqxmd.com/read/28488122/the-potential-of-cellular-and-viral-based-immunotherapies-for-malignant-glioma-dendritic-cell-vaccines-adoptive-cell-transfer-and-oncolytic-viruses
#10
REVIEW
Russell Maxwell, Andrew S Luksik, Tomas Garzon-Muvdi, Michael Lim
PURPOSE OF REVIEW: Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses. RECENT FINDINGS: Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma...
June 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28480328/preclinical-safety-studies-of-enadenotucirev-a-chimeric-group-b-human-specific-oncolytic-adenovirus
#11
Sam Illingworth, Ying Di, Maxine Bauzon, Janet Lei, Margaret R Duffy, Simon Alvis, Brian Champion, André Lieber, Terry Hermiston, Len W Seymour, John Beadle, Kerry Fisher
Enadenotucirev is an oncolytic group B adenovirus identified by a process of bio-selection for the ability to selectively propagate in and rapidly kill carcinoma cells. It is resistant to inactivation by human blood components, potentially enabling intravenous dosing in patients with metastatic cancer. However, there are no known permissive animal models described for group B adenoviruses that could facilitate a conventional approach to preclinical safety studies. In this manuscript, we describe our tailored preclinical strategy designed to evaluate the key biological properties of enadenotucirev...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28480327/humanized-mice-with-subcutaneous-human-solid-tumors-for-immune-response-analysis-of-vaccinia-virus-mediated-oncolysis
#12
Desislava Tsoneva, Boris Minev, Alexa Frentzen, Qian Zhang, Anja K Wege, Aladar A Szalay
Oncolytic vaccinia virus (VACV) therapy is an alternative cancer treatment modality that mediates targeted tumor destruction through a tumor-selective replication and an induction of anti-tumor immunity. We developed a humanized tumor mouse model with subcutaneous human tumors to analyze the interactions of VACV with the developing tumors and human immune system. A successful systemic reconstitution with human immune cells including functional T cells as well as development of tumors infiltrated with human T and natural killer (NK) cells was observed...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28480326/combining-oncolytic-virotherapy-with-p53-tumor-suppressor-gene-therapy
#13
REVIEW
Christian Bressy, Eric Hastie, Valery Z Grdzelishvili
Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28480325/the-sequence-of-delta24-rgd-and-tmz-administration-in-malignant-glioma-affects-the-role-of-cd8-t-cell-anti-tumor-activity
#14
Anne Kleijn, Wouter van den Bossche, Erik S Haefner, Zineb Belcaid, Chantal Burghoorn-Maas, Jenneke J Kloezeman, Suzan D Pas, Sieger Leenstra, Reno Debets, Jeroen de Vrij, Clemens M F Dirven, Martine L M Lamfers
The conditionally replicating oncolytic adenovirus Delta24-RGD (Ad) is currently under investigation in clinical trials for glioblastoma, including in combination with temozolomide (TMZ), the standard chemotherapy for this tumor. Previously, we showed that the efficacy of Delta24-RGD in a murine model is primarily dependent on the virus-induced anti-tumor immune response. As observed with most chemotherapies, TMZ has pronounced immune-modulating effects. Here, we studied the combined effects of these treatments in a murine glioma model...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28480304/viral-vector-based-innovative-approaches-to-directly-abolishing-tumorigenic-pluripotent-stem-cells-for-safer-regenerative-medicine
#15
REVIEW
Kaoru Mitsui, Kanako Ide, Tomoyuki Takahashi, Ken-Ichiro Kosai
Human pluripotent stem cells (hPSCs) are a promising source of regenerative material for clinical applications. However, hPSC transplant therapies pose the risk of teratoma formation and malignant transformation of undifferentiated remnants. These problems underscore the importance of developing technologies that completely prevent tumorigenesis to ensure safe clinical application. Research to date has contributed to establishing safe hPSC lines, improving the efficiency of differentiation induction, and indirectly ensuring the safety of products...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28479936/presage-of-oncolytic-virotherapy-for-oral-cancer-with-herpes-simplex-virus
#16
REVIEW
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
https://www.readbyqxmd.com/read/28466296/t-independent-response-mediated-by-oncolytic-tanapoxvirus-recombinants-expressing-interleukin-2-and-monocyte-chemoattractant-protein-1-suppresses-human-triple-negative-breast-tumors
#17
Yogesh R Suryawanashi, Tiantian Zhang, Helene M Woyczesczyk, John Christie, Emily Byers, Steven Kohler, Robert Eversole, Charles Mackenzie, Karim Essani
Human triple negative breast cancer (TNBC) is an aggressive disease, associated with a high rate of recurrence and metastasis. Current therapeutics for TNBC are limited, highly toxic and show inconsistent efficacy due to a high degree of intra-tumoral and inter-tumoral heterogeneity. Oncolytic viruses (OVs) are an emerging treatment option for cancers. Several OVs are currently under investigation in preclinical and clinical settings. Here, we examine the oncolytic potential of two tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP)-1 [also known as mCCL2] and mouse interleukin (mIL)-2, in human TNBC, in vitro and in vivo...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28465492/oncolytic-efficacy-of-thymidine-kinase-deleted-vaccinia-virus-strain-guang9
#18
Lili Deng, Jun Fan, Yuedi Ding, Jue Zhang, Bin Zhou, Yi Zhang, Biao Huang
Oncolytic virotherapy is being developed as a promising platform for cancer therapy due to its ability to lyse cancer cells in a tumor-specific manner. Vaccinia virus has been used as a live vaccine in the smallpox eradication program and now is being potential in cancer therapy with a great safety profile. Vaccinia strain Guang9 (VG9) is an attenuated Chinese vaccinia virus and its oncolytic efficacy has been evaluated in our previous study. To improve the tumor selectivity and oncolytic efficacy, we here developed a thymidine kinase (TK)-deleted vaccinia virus based on Guang9 strain...
April 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465158/measles-virus-hemagglutinin-epitopes-immunogenic-in-natural-infection-and-vaccination-are-targeted-by-broad-or-genotype-specific-neutralizing-monoclonal-antibodies
#19
Miguel Angel Muñoz-Alía, José M Casasnovas, María Luisa Celma, Juan Carabaña, Paloma B Liton, Rafael Fernandez-Muñoz
Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia)...
April 29, 2017: Virus Research
https://www.readbyqxmd.com/read/28464762/cancer-targeted-oncolytic-adenoviruses-for-modulation-of-the-immune-system
#20
Vincenzo Cerullo, Cristian Capasso, Markus Vähä-Koskela, Otto Hemminki, Akseli Hemminki
Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen-presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit...
May 2, 2017: Current Cancer Drug Targets
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