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Oncolytic viral therapy

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https://www.readbyqxmd.com/read/29034314/targeting-an-oncolytic-influenza-a-virus-to-tumor-tissue-by-elastase
#1
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
#2
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...
October 6, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28955655/oncolytic-viruses-natural-and-genetically-engineered-cancer-immunotherapies
#3
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
#4
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
#5
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
#6
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-as-48
#7
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 Z-d-Phe-l-Phe Gly (fusion inhibitor peptide, FIP) and AS-48 have similar efficacy in blocking membrane fusion and syncytia formation mediated by measles virus. 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 which were resistant to the inhibitory effects of Z-d-Phe-l-Phe Gly. These 10 mutations were localized to the heptad repeat region (HRB) of the fusion protein and no changes were observed in the viral hemagglutinin, which is the receptor attachment protein...
September 13, 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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28814886/a-practical-guide-to-the-handling-and-administration-of-talimogene-laherparepvec-in-europe
#13
REVIEW
Kevin J Harrington, Olivier Michielin, Josep Malvehy, Isabella Pezzani Grüter, Lorna Grove, Anna Lisa Frauchiger, Reinhard Dummer
Talimogene laherparepvec is a herpes simplex virus-1-based intralesional oncolytic immunotherapy and is the first oncolytic virus to be approved in Europe. It is indicated for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (stage IIIB, IIIC, and IVM1a) with no bone, brain, lung, or other visceral disease. Talimogene laherparepvec is a genetically modified viral therapy, and its handling needs special attention due to its deep freeze, cold-chain requirements, its potential for viral shedding, and its administration by direct intralesional injection...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28801903/synthetic-tumor-specific-promoters-for-transcriptional-regulation-of-viral-replication
#14
Maria Veronica Lopez, Eduardo G Cafferata, Diego L Viale, Osvaldo L Podhajcer
Here we describe a collection of methods that have been adapted to isolate and modify tumor-specific promoters (TSPs ) to drive viral replication for cancer therapy and other uses. We will describe as examples the secreted protein acidic and rich in cysteine (SPARC ) and the protease-activated receptor-1 (PAR-1) promoter. We outline strategies to select appropriate TSPs using bioinformatics resources and the methods utilized in their subsequent cloning, assessment of transcriptional activity, and their use in conditionally replicative oncolytic adenoviruses ...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28796161/comparison-of-liver-detargeting-strategies-for-systemic-therapy-with-oncolytic-adenovirus-serotype-5
#15
Tien V Nguyen, Mary E Barry, Mallory A Turner, Catherine M Crosby, Miguel A Trujillo, John C Morris, Michael A Barry
Oncolytic viruses would ideally be of use for systemic therapy to treat disseminated cancer. To do this safely, this may require multiple layers of cancer specificity. The pharmacology and specificity of oncolytic adenoviruses can be modified by (1) physical retargeting, (2) physical detargeting, (3) chemical shielding, or (4) by modifying the ability of viral early gene products to selectively activate in cancer versus normal cells. We explored the utility of these approaches with oncolytic adenovirus serotype 5 (Ad5) in immunocompetent Syrian hamsters bearing subcutaneous HaK tumors...
August 10, 2017: Biomedicines
https://www.readbyqxmd.com/read/28793793/making-oncolytic-virotherapy-a-clinical-reality-the-european-contribution
#16
Margaret R Duffy, Kerry D Fisher, Len W Seymour
Oncolytic viruses (OVs) are quickly moving toward the forefront of modern medicines. The reward for the decades of research invested into developing viral platforms that selectively replicate in and lyse tumor cells while sparking anticancer adaptive immunity is presenting in the form of durable therapeutic responses. While this has certainly been a concerted global effort, in this review for the 25th anniversary of the European Society of Gene and Cell Therapy, we focus on the contributions made by European researchers...
August 1, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28738050/intralesional-therapy-consensus-statements-for-best-practices-in-administration-from-the-melanoma-nursing-initiative%C3%A2
#17
Virginia Seery
BACKGROUND: Talimogene laherparepvec (T-VEC) is the first intralesional therapy for melanoma approved by the U.S. Food and Drug Administration. This oncolytic viral immunotherapy has improved outcomes for patients with locoregional recurrent melanoma and is showing promise in combination with systemic therapies. 
. OBJECTIVES: This article aims to provide oncology nurses with expert guidance on best practices in incorporating intralesional therapy for patients diagnosed with melanoma in practice...
August 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28725635/implications-of-micrornas-in-oncolytic-virotherapy
#18
REVIEW
Xavier Bofill-De Ros, Maria Rovira-Rigau, Cristina Fillat
MicroRNAs (miRNAs) are an abundant class of small non-coding RNA molecules (~22 nt) that can repress gene expression. Deregulation of certain miRNAs is widely recognized as a robust biomarker for many neoplasms, as well as an important player in tumorigenesis and the establishment of tumoral microenvironments. The downregulation of specific miRNAs in tumors has been exploited as a mechanism to provide selectivity to oncolytic viruses or gene-based therapies. miRNA response elements recognizing miRNAs expressed in specific tissues, but downregulated in tumors, have been inserted into the 3'UTR of viral genes to promote the degradation of these viral mRNAs in healthy tissue, but not in tumor cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28724773/nkp46-recognizes-the-sigma1-protein-of-reovirus-implications-for-reovirus-based-cancer-therapy
#19
Yotam Bar-On, Yoav Charpak-Amikam, Ariella Glasner, Batya Isaacson, Alexandra Duev-Cohen, Pinchas Tsukerman, Alexander Varvak, Michal Mandelboim, Ofer Mandelboim
The recent approval of oncolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK cell-activating receptor NKp46 and the orthologous mouse protein NCR1 recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify sites of NKp46/NCR1 binding to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation in vitro Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy in vivo Collectively, we have identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed both for clearance of reovirus infection and for reovirus-based tumor therapy...
October 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28713676/immunotherapy-for-malignant-pleural-mesothelioma-current-status-and-future-directions
#20
REVIEW
Jordan Dozier, Hua Zheng, Prasad S Adusumilli
Malignant pleural mesothelioma (MPM) has been marked historically by poor prognosis. Current standard of care for this deadly disease results in sub-optimal improvements in overall survival (OS), which has prompted researchers to explore innovative treatment alternatives. Immunotherapy is an emerging therapeutic modality that harnesses the power of the human immune system. In this review, we summarize the different methods of immunotherapy for malignant pleural mesothelioma. Using ClinicalTrials.gov we searched the terms "immunotherapy" and "immune therapy" combined with "pleural mesothelioma"...
June 2017: Translational Lung Cancer Research
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