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Oncolytic viral therapy

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https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#1
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 Δγ134.5 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...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29200874/simultaneous-overexpression-of-mir-126-and-mir-34a-induces-a-superior-antitumor-efficacy-in-pancreatic-adenocarcinoma
#2
Shu-De Feng, Ziming Mao, Chunying Liu, Yu-Song Nie, Bin Sun, Minggao Guo, Changqing Su
Background: Pancreatic adenocarcinoma (PAC) is one of the most fatal cancers due to its high degree of malignancy, increasing incidence, high mortality, and unsatisfactory treatment efficacy. Evidence has suggested that numerous microRNAs (miRNAs), including miR-126 and miR-34a, have potent tumor-suppressing effects on PAC, implicating a possible application of miRNA in tumor therapy. However, the therapeutic effect of a single miRNA on pancreatic cancer is limited. Methods: We simultaneously delivered miR-126 and miR-34a into PAC cells by a carcinoembryonic antigen promoter-driven oncolytic adenovirus (AdCEAp-miR126/34a), and examined the antitumor efficacy of the therapeutic system in in vitro and in vivo experiments...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29179527/hitting-the-nail-on-the-head-combining-oncolytic-adenovirus-mediated-virotherapy-and-immunomodulation-for-the-treatment-of-glioma
#3
REVIEW
Wojciech K Panek, J Robert Kane, Jacob S Young, Aida Rashidi, Julius W Kim, Deepak Kanojia, Maciej S Lesniak
Glioblastoma is a highly aggressive malignant brain tumor with a poor prognosis and the median survival 14.6 months. Immunomodulatory proteins and oncolytic viruses represent two treatment approaches that have recently been developed for patients with glioblastoma that could extend patient survival and result in better treatment outcomes for patients with this disease. Together, these approaches could potentially augment the treatment efficacy and strength of these anti-tumor therapies. In addition to oncolytic activities, this combinatory approach introduces immunomodulation locally only where cancerous cells are present...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29179469/bioluminescence-imaging-of-a-tumor-selective-thymidine-kinase-defective-vaccinia-virus-guang9-strain-after-intratumoral-or-intraperitoneal-administration-in-mice
#4
Yuedi Ding, Jun Fan, Lili Deng, Ying Peng, Jue Zhang, Biao Huang
Vaccinia virus has been used as an oncolytic virus because of its capacity to preferentially infect tumors rather than normal tissues. The vaccinia Tian Tan strain, used as a vaccine against smallpox for millions of people in China, is a promising candidate for cancer therapy. In this study, we constructed an attenuated Tian Tan strain of Guang9 with a disrupted thymidine kinase gene to enhance tumor selectivity and an inserted firefly luciferase to monitor the viral distribution by in vivo bioluminescence imaging...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29169830/rapamycin-enhances-lytic-replication-of-epstein-barr-virus-in-gastric-carcinoma-cells-by-increasing-the-transcriptional-activities-of-immediate-early-lytic-promoters
#5
Man Wang, Wei Wu, Yinfeng Zhang, Guoliang Yao, Bianli Gu
Epstein-Barr virus (EBV), a human herpesvirus, is linked to both epithelial and lymphoid malignancies. Induction of EBV reactivation is a potential therapeutic strategy for EBV-associated tumors. In this study, we assessed the effects of rapamycin on EBV reactivation in gastric carcinoma cells. We found that rapamycin upregulated expression of EBV lytic proteins and increased the viral proliferation triggered by the EBV lytic inducer sodium butyrate. Reverse transcription-qPCR, luciferase activity assays, chromatin immunoprecipitation and western blotting were employed to explore the mechanism by which rapamycin promotes EBV reactivation...
November 20, 2017: Virus Research
https://www.readbyqxmd.com/read/29156834/oncolytic-reovirus-inhibits-angiogenesis-through-induction-of-cxcl10-ip-10-and-abrogation-of-hif-activity-in-soft-tissue-sarcomas
#6
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Monica M Mita, Alain C Mita, Steffan T Nawrocki
The tumor-selective viral replication capacity and pro-apoptotic effects of oncolytic reovirus have been reported to be dependent on the presence of an activated RAS pathway in several solid tumor types. However, the mechanisms of selective anticancer efficacy of the reovirus-based formulation for cancer therapy (Reolysin, pelareorep) have not been rigorously studied in soft tissue sarcomas (STS). Here we report that Reolysin triggered a striking induction of the anti-angiogenic chemokine interferon-γ-inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) in both wild type and RAS mutant STS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29146945/maraba-virus-vectored-cancer-vaccines-represent-a-safe-and-novel-therapeutic-option-for-cats
#7
Jeff Hummel, Dorothee Bienzle, Annette Morrison, Michelle Cieplak, Kyle Stephenson, Josepha DeLay, J Paul Woods, Brian D Lichty, Byram W Bridle
Direct killing of malignant cells combined with induction of tumour-specific immune responses makes oncolytic vaccines attractive for cancer therapy. We previously developed a heterologous cancer immunization strategy that utilized a replication-defective adenovirus-vectored primary vaccine encoding a tumour antigen followed by boosting with a replication-competent Maraba virus expressing the same antigen. To assess the safety of oncolytic Maraba virus-based booster vaccines and inform the design of clinical trials, we conducted translational studies in cats, which have immune systems that are similar to people and spontaneously develop cancers of comparable types and etiologies...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29076241/oncolytic-reovirus-therapy-pilot-study-in-dogs-with-spontaneously-occurring-tumours
#8
C C Hwang, M Igase, M Sakurai, T Haraguchi, K Tani, K Itamoto, T Shimokawa, M Nakaichi, Y Nemoto, S Noguchi, M Coffey, M Okuda, T Mizuno
Oncolytic virotherapy is a novel treatment involving replication-competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 10(8) to 5.0 × 10(9) TCID50 given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles...
October 27, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29034314/targeting-an-oncolytic-influenza-a-virus-to-tumor-tissue-by-elastase
#9
Irina Kuznetsova, Tobias Arnold, Thomas Aschacher, Cornelia Schwager, Balazs Hegedus, Tamas Garay, Marina Stukova, Maria Pisareva, Stephan Pleschka, Michael Bergmann, Andrej Egorov
Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28984290/role-of-autophagy-in-oncolytic-herpes-simplex-virus-type-1-induced-cell-death-in-squamous-cell-carcinoma-cells
#10
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
https://www.readbyqxmd.com/read/28955655/oncolytic-viruses-natural-and-genetically-engineered-cancer-immunotherapies
#11
REVIEW
Sachin R Jhawar, Aditya Thandoni, Praveen K Bommareddy, Suemair Hassan, Frederick J Kohlhapp, Sharad Goyal, Jason M Schenkel, Ann W Silk, Andrew Zloza
There has long been interest in innovating an approach by which tumor cells can be selectively and specifically targeted and destroyed. The discovery of viruses that lyse tumor cells, termed oncolytic viruses (OVs), has led to a revolution in the treatment of cancer. The potential of OVs to improve the therapeutic ratio is derived from their ability to preferentially infect and replicate in cancer cells while avoiding destruction of normal cells surrounding the tumor. Two main mechanisms exist through which these viruses are reported to improve outcomes: direct lysis of tumor cells and indirect augmentation of host anti-tumor immunity...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28940544/chronic-granulomatous-dermatitis-induced-by-talimogene-laherparepvec-therapy-of-melanoma-metastases
#12
Ashlyn S Everett, Peter G Pavlidakey, Carlo M Contreras, Jennifer F De Los Santos, Ju Y Kim, Svetlana B McKee, Howard L Kaufman, Robert M Conry
Talimogene laherparepvec is the first oncolytic viral immunotherapy approved by the FDA, for advanced melanoma consisting of genetically modified herpes simplex type 1 virus which selectively replicates causing tumor lysis, expressing GM-CSF and activating dendritic cells. Intratumoral injection of TVEC produces objective response in 41% of stage IIB-IV M1a melanoma. However, clinical response assessments can be problematic due to immune-related inflammation at established tumor sites. Herein, we report 5 cases of granulomatous dermatitis developing at sites of TVEC injection associated with pathologic complete response in 4 of 5 patients...
September 22, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28934149/oncolytic-reovirus-infection-is-facilitated-by-the-autophagic-machinery
#13
Vera Kemp, Iris J C Dautzenberg, Ronald W Limpens, Diana J M van den Wollenberg, Rob C Hoeben
Mammalian reovirus is a double-stranded RNA virus that selectively infects and lyses transformed cells, making it an attractive oncolytic agent. Despite clinical evidence for anti-tumor activity, its efficacy as a stand-alone therapy remains to be improved. The success of future trials can be greatly influenced by the identification and the regulation of the cellular pathways that are important for reovirus replication and oncolysis. Here, we demonstrate that reovirus induces autophagy in several cell lines, evident from the formation of Atg5-Atg12 complexes, microtubule-associated protein 1 light chain 3 (LC3) lipidation, p62 degradation, the appearance of acidic vesicular organelles, and LC3 puncta...
September 21, 2017: Viruses
https://www.readbyqxmd.com/read/28922411/cytokine-induced-killer-cell-delivery-enhances-the-antitumor-activity-of-oncolytic-reovirus
#14
Xing Zhao, Weiwei Ouyang, Cariad Chester, Shiqi Long, Nianxue Wang, Zhixu He
Oncolytic viruses (OV) have recently emerged as a promising therapeutic modality in cancer treatment. OV selectively infect and kill tumor cells, while sparing untransformed cells. The direct cytotoxic effects combined with the capacity to trigger an immune response make OV an appealing combination partner in the burgeoning field of cancer immunotherapy. One of the leading OV therapeutic candidates is the double-stranded RNA virus reovirus. In order to improve the oncolytic activity of reovirus and allow for systemic administration despite the prevalence of neutralizing antibodies, cytokine-induced killer (CIK) cells were explored as cell carriers for reovirus delivery...
2017: PloS One
https://www.readbyqxmd.com/read/28904193/mutations-in-the-fusion-protein-of-measles-virus-that-confer-resistance-to-the-membrane-fusion-inhibitors-carbobenzoxy-d-phe-l-phe-gly-and-4-nitro-2-phenylacetyl-amino-benzamide
#15
Michael N Ha, Sébastien Delpeut, Ryan S Noyce, Gary Sisson, Karen M Black, Liang-Tzung Lin, Darius Bilimoria, Richard K Plemper, Gilbert G Privé, Christopher D Richardson
The inhibitors carbobenzoxy (Z)-d-Phe-l-Phe-Gly (fusion inhibitor peptide [FIP]) and 4-nitro-2-phenylacetyl amino-benzamide (AS-48) have similar efficacies in blocking membrane fusion and syncytium formation mediated by measles virus (MeV). Other homologues, such as Z-d-Phe, are less effective but may act through the same mechanism. In an attempt to map the site of action of these inhibitors, we generated mutant viruses that were resistant to the inhibitory effects of Z-d-Phe-l-Phe-Gly. These 10 mutations were localized to the heptad repeat B (HRB) region of the fusion protein, and no changes were observed in the viral hemagglutinin, which is the receptor attachment protein...
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28893277/development-of-an-hiv-vaccine-using-a-vesicular-stomatitis-virus-vector-expressing-designer-hiv-1-envelope-glycoproteins-to-enhance-humoral-responses
#16
REVIEW
Trina Racine, Gary P Kobinger, Eric J Arts
Vesicular stomatitis virus (VSV), like many other Rhabdoviruses, have become the focus of intense research over the past couple of decades based on their suitability as vaccine vectors, transient gene delivery systems, and as oncolytic viruses for cancer therapy. VSV as a vaccine vector platform has multiple advantages over more traditional viral vectors including low level, non-pathogenic replication in diverse cell types, ability to induce both humoral and cell-mediate immune responses, and the remarkable expression of foreign proteins cloned into multiple intergenic sites in the VSV genome...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28884088/oncolytic-viral-therapy-for-mesothelioma
#17
REVIEW
Daniel F Pease, Robert A Kratzke
The limited effectiveness of conventional therapy for malignant pleural mesothelioma demands innovative approaches to this difficult disease. Even with aggressive multimodality treatment of surgery, radiation, and/or chemotherapy, the median survival is only 1-2 years depending on stage and histology. Oncolytic viral therapy has emerged in the last several decades as a rapidly advancing field of immunotherapy studied in a wide spectrum of malignancies. Mesothelioma makes an ideal candidate for studying oncolysis given the frequently localized pattern of growth and pleural location providing access to direct intratumoral injection of virus...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28854921/spatial-and-temporal-epithelial-ovarian-cancer-cell-heterogeneity-impacts-maraba-virus-oncolytic-potential
#18
Jessica G Tong, Yudith Ramos Valdes, Milani Sivapragasam, John W Barrett, John C Bell, David Stojdl, Gabriel E DiMattia, Trevor G Shepherd
BACKGROUND: Epithelial ovarian cancer exhibits extensive interpatient and intratumoral heterogeneity, which can hinder successful treatment strategies. Herein, we investigated the efficacy of an emerging oncolytic, Maraba virus (MRBV), in an in vitro model of ovarian tumour heterogeneity. METHODS: Four ovarian high-grade serous cancer (HGSC) cell lines were isolated and established from a single patient at four points during disease progression. Limiting-dilution subcloning generated seven additional subclone lines to assess intratumoral heterogeneity...
August 30, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28842478/leucine-rich-repeat-containing-g-protein-coupled-receptor-4-facilitates-vesicular-stomatitis-virus-infection-by-binding-vesicular-stomatitis-virus-glycoprotein
#19
Na Zhang, Hongjun Huang, Binghe Tan, Yinglei Wei, Qingqing Xiong, Yan Yan, Lili Hou, Nannan Wu, Stefan Siwko, Andrea Cimarelli, Jianrong Xu, Honghui Han, Min Qian, Mingyao Liu, Bing Du
Vesicular stomatitis virus (VSV) and rabies and Chandipura viruses belong to the Rhabdovirus family. VSV is a common laboratory virus to study viral evolution and host immune responses to viral infection, and recombinant VSV-based vectors have been widely used for viral oncolysis, vaccination, and gene therapy. Although the tropism of VSV is broad, and its envelope glycoprotein G is often used for pseudotyping other viruses, the host cellular components involved in VSV infection remain unclear. Here, we demonstrate that the host protein leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is essential for VSV and VSV-G pseudotyped lentivirus (VSVG-LV) to infect susceptible cells...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28838332/oncolytic-e1b-55kda-deleted-adenovirus-replication-is-independent-of-p53-levels-in-cancer-cells
#20
B M Abbas, M A El-Mogy, Y Haj-Ahmad
Oncolytic adenoviruses represent a new approach for cancer therapy due to its tumor specificity. E1B 55kDa-deleted adenovirus type 5 (Ad5dlE1B 55kDa) is a promising therapeutic agent that can selectively replicate in and lyse p53 defective cancer cells. However, the overall efficacy has shown varying degrees of success with raised doubts about the correlation between p53 status and E1B-deleted adenovirus replication ability. In this study, we investigated the relationship between the efficiency of Ad5dlE1B 55kDa replication and p53 levels in cancer cells...
August 15, 2017: Cellular and Molecular Biology
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