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Oncolytic viruses

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https://www.readbyqxmd.com/read/28725635/implications-of-micrornas-in-oncolytic-virotherapy
#1
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
#2
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 onclolytic 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 activating receptor, NKp46, and its mouse orthologous protein, NCR1, recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify NKp46/NCR1 binding sites 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 identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed for both clearance of reovirus infections and reovirus-based tumor therapy...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28720686/oncolytic-virus-induced-cell-death-and-immunity-a-match-made-in-heaven
#3
REVIEW
Jolien De Munck, Alex Binks, Iain A McNeish, Joeri L Aerts
Our understanding of the mechanisms responsible for cancer development has increased enormously over the last decades. However, for many cancers, this has not been translated into a significant improvement in overall survival, and overall mortality remains high. Treatment for many malignancies remains based on surgery, chemotherapy, and radiotherapy. Significant progress has been made toward the development of more specific, more potent, and less invasive treatment modalities, but such targeted therapies remain the exception for most cancers...
July 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28716945/evaluating-optimal-therapy-robustness-by-virtual-expansion-of-a-sample-population-with-a-case-study-in-cancer-immunotherapy
#4
Syndi Barish, Michael F Ochs, Eduardo D Sontag, Jana L Gevertz
Cancer is a highly heterogeneous disease, exhibiting spatial and temporal variations that pose challenges for designing robust therapies. Here, we propose the VEPART (Virtual Expansion of Populations for Analyzing Robustness of Therapies) technique as a platform that integrates experimental data, mathematical modeling, and statistical analyses for identifying robust optimal treatment protocols. VEPART begins with time course experimental data for a sample population, and a mathematical model fit to aggregate data from that sample population...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716652/toxicity-profiles-of-immunotherapy
#5
REVIEW
Sophie Cousin, Antoine Italiano
Immunotherapies are changing the landscape of advanced solid tumor treatment. These therapies have different mechanisms of action and include oncolytic viruses, checkpoint inhibitors, such as CTLA-4 or PD1/PD-L1 monoclonal antibodies, and CSF-1R antibodies. Given the growing therapeutic impact of these agents in oncology, it is important to better understand their properties. Immunotherapies generate new toxicity profiles that are called immune-related adverse events and require specific management. This review focuses on the mechanisms of action of such side effects, as well as their description and their general management...
July 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28712033/oncolytic-immunotherapy-unlocking-the-potential-of-viruses-to-help-target-cancer
#6
REVIEW
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)...
July 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28711493/anti-cancer-effect-of-oncolytic-adenovirus-armed-shrna-targeting-mycn-gene-on-doxorubicin-resistant-neuroblastoma-cells
#7
Yuan Li, Baobiao Zhuo, Yiyu Yin, Tao Han, Shixian Li, Zhengwei Li, Jian Wang
Chemotherapy is one of the few effective choices for patients with neuroblastoma. However, the development of muti-drug resistance (MDR) to chemotherapy is a major obstacle to the effective treatment of advanced or recurrent neuroblastoma. The muti-drug resistance-associated protein (MRP), which encodes a transmembrane glycoprotein, is a key regulator of MDR. The expression of MRP is a close correlation with MYCN oncogene in neuroblastoma. We have recently shown ZD55-shMYCN (oncolytic virus armed with shRNA against MYCN) can down-regulate MYCN to inhibit tumor cells proliferation and induce apoptosis in neuroblastoma...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710334/stem-cell-released-oncolytic-herpes-simplex-virus-has-therapeutic-efficacy-in-brain-metastatic-melanomas
#8
Wanlu Du, Ivan Seah, Oumaima Bougazzoul, GiHun Choi, Katrina Meeth, Marcus W Bosenberg, Hiroaki Wakimoto, David Fisher, Khalid Shah
The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs)...
July 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28706012/local-delivery-of-oncovex-mgm-csf-generates-systemic-anti-tumor-immune-responses-enhanced-by-cytotoxic-t-lymphocyte-associated-protein-blockade
#9
Achim K Moesta, Keegan Cooke, Julia Piasecki, Petia Mitchell, James B Rottman, Karen Fitzgerald, Jinghui Zhan, Becky Yang, Tiep Le, Brian Belmontes, Oluwatayo F Ikotun, Kim Merriam, Charles Glaus, Kenneth Ganley, David H Cordover, Andrea M Boden, Rafael Ponce, Courtney Beers, Pedro J Beltran
Talimogene laherparepvec, a new oncolytic immunotherapy, has been recently approved for the treatment of melanoma. Using a murine version of the virus we characterized local and systemic anti-tumor immune responses driving efficacy in murine syngeneic models.<br /><br />Experimental Design: The activity of talimogene laherparepvec was characterized against melanoma cell lines using an in vitro viability assay. Efficacy of OncoVEX(mGM-CSF) (talimogene laherparepvec with the mouse granulocyte-macrophage colony-stimulating factor transgene) alone or in combination with checkpoint blockade was characterized in A20 and CT-26 contralateral murine tumor models...
July 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28702840/oncolytic-viruses-adenoviruses
#10
REVIEW
Julia Niemann, Florian Kühnel
Tumor-selectively replicating (oncolytic) viruses are promising tools for therapy of solid cancers and have been initially developed to achieve potent tumor lysis with acceptable side effects on healthy tissue. However, in recent years, oncolytic viruses have been recognized as therapeutic vehicles exhibiting multipronged anti-tumoral activity. Apart from direct cytolysis, stimulation of both innate and adaptive tumor-directed immune responses have been recognized as important mechanisms of oncolytic virotherapy, which were probably decisive in achieving the long-term tumor remissions that oncolytic viruses have shown in clinical trials in advanced melanoma...
July 12, 2017: Virus Genes
https://www.readbyqxmd.com/read/28701757/oncolytic-measles-virus-enhances-antitumour-responses-of-adoptive-cd8-nkg2d-cells-in-hepatocellular-carcinoma-treatment
#11
Aiping Chen, Yonghui Zhang, Gang Meng, Dengxu Jiang, Hailin Zhang, Meihong Zheng, Mao Xia, Aiqin Jiang, Junhua Wu, Christian Beltinger, Jiwu Wei
There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8(+)NKG2D(+) cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8(+)NKG2D(+) cells, mediated by at least three distinct mechanisms...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698504/impact-of-autophagy-in-oncolytic-adenoviral-therapy-for-cancer
#12
REVIEW
Hiroshi Tazawa, Shinji Kuroda, Joe Hasei, Shunsuke Kagawa, Toshiyoshi Fujiwara
Oncolytic virotherapy has recently emerged as a promising strategy for inducing tumor-specific cell death. Adenoviruses are widely and frequently used in oncolytic virotherapy. The mechanism of oncolytic adenovirus-mediated tumor suppression involves virus-induced activation of the autophagic machinery in tumor cells. Autophagy is a cytoprotective process that produces energy via lysosomal degradation of intracellular components as a physiologic response to various stresses, including hypoxia, nutrient deprivation, and disruption of growth signaling...
July 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28687873/%C3%AE-2-6-linked-sialic-acid-serves-as-a-high-affinity-receptor-for-cancer-oncolytic-virotherapy-with-newcastle-disease-virus
#13
Qian Li, Ding Wei, Fei Feng, Xi-Long Wang, Can Li, Zhi-Nan Chen, Huijie Bian
PURPOSE: Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property. In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated. METHODS: Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor...
July 7, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28679779/molecular-effects-of-stromal-selective-targeting-by-upar-retargeted-oncolytic-virus-in-breast-cancer
#14
Yuqi Jing, Valery Chavez, Yuguang Ban, Nicolas Acquavella, Dorraya El-Ashry, Alexey Pronin, Xi Chen, Jaime R Merchan
The tumor microenvironment (TME) is a relevant target for novel biological therapies. MV-m-uPA and MV-h-uPA are fully retargeted, species-specific, oncolytic measles viruses (MVs) directed against murine or human urokinase receptor (PLAUR/uPAR), expressed in tumor and stromal cells. The effects of stromal selective targeting by uPAR retargeted MVs were investigated. In vitro infection, virus-induced GFP expression and cytotoxicity by MV-h-uPA and MV-m-uPA were demonstrated in human and murine cancer cells and cancer associated fibroblasts (CAFs) in a species-specific manner...
July 5, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28679776/phase-i-trial-of-intravenous-oncolytic-vaccinia-virus-gl-onc1-with-cisplatin-and-radiotherapy-in-patients-with-locoregionally-advanced-head-and-neck-carcinoma
#15
Loren K Mell, Kevin T Brumund, Gregory A Daniels, Sunil J Advani, Kaveh Zakeri, Mary E Wright, Sara-Jane Onyeama, Robert A Weisman, Parag R Sanghvi, Peter J Martin, Aladar A Szalay
Pre-clinical models have shown that the effectiveness of GL-ONC1, a modified <p>oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study</p> <p>was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy</p> <p>to patients with primary, non-metastatic head and neck cancer.</p> <p>EXPERIMENTAL DESIGN: Patients with locoregionally advanced unresected, non-metastatic</p> <p>carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were</p> <p>treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and</p> <p>chemotherapy...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28678032/therapeutic-oncolytic-viruses-clinical-advances-and-future-directions
#16
Susanne G Warner, Michael P O'Leary, Yuman Fong
PURPOSE OF REVIEW: The present review will highlight recent advances in the clinical application of oncolytic viral therapy. RECENT FINDINGS: Until recently, oncolytic viral researchers saw the immune system as an enemy that would clear the virus from the bloodstream. However, researchers now understand that sustained responses are seen in those patients with more robust antitumor immune responses. Much of the current focus in oncolytic viral research is trained on manipulation of the immune system to affect cancer cell killing in the tumor microenvironment and to facilitate durable systemic antitumor immunity...
July 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28672936/apoptosis-inducing-effect-of-myxoma-virus-on-human-neuroglioma-cell-lines
#17
Qiu-Sheng Zhang, Meng Zhang, Xian-Jian Huang, Xiao-Jia Liu, Wei-Ping Li
The purpose of this study was to further evaluate the role of myxoma virus (MYXV) as an oncolytic agent against experimental human gliomas in vitro, and analyze the effect of MYXV on malignant glioma cells at different incubation periods and infected at different multiplicities of infection. Neuroglioma cell lines U251 and A172 were cultured with various infective doses of myxoma virus at different time points (0-3 days) and cellular survival rates were evaluated using an MTT assay. Cell viability and cell death rates were assessed using Annexin V/propidium iodide and applying flow cytometry...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28670384/a-dual-regulated-oncolytic-adenovirus-carrying-tap63-gene-exerts-potent-antitumor-effect-on-colorectal-cancer-cells
#18
Qifeng Luo, Heying Liu, Zhenyu Zhang, Shiva Basnet, Zhenling Dai, Shuping Li, Yuxiang Wang, Bin Xu, Haiyan Ge
The purpose of this study is to evaluate possible antitumor activity of a dual-regulated oncolytic adenovirus carrying the TAp63 gene on colorectal cancer. The recombinant virus Ad-survivin-ZD55-TAp63 was constructed by inserting the TAp63 gene into the dual-regulated pshuttle-survivin-ZD55 vector. RT-PCR and western blot assays were used to verify the recombinant virus Ad-survivin-ZD55-TAp63. Crystal violet staining was carried out to detect the cytopathic effect of Ad-survivin-ZD55-TAp63 in human colorectal cancer cell line HCT-116 and normal liver cell line L-O2...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28669340/oncolytic-tanapoxvirus-expressing-interleukin-2-is-capable-of-inducing-the-regression-of-human-melanoma-tumors-in-the-absence-of-t-cells
#19
Tiantian Zhang, Dennis H Kordish, Yogesh R Suryawanshi, Rob R Eversole, Steven Kohler, Charles D Mackenzie, Karim Essani
Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-2 (IL-2), a T-cell growth factor, plays a critical role in activating T cells, natural killer (NK) cells and macrophages in both the innate and adaptive immune system. In this study, a recombinant TANV expressing mouse IL-2 (TANVΔ66R/mIL-2) was generated, where the viral thymidine kinase (TK) gene (66R) was replaced with the mIL-2 transgene...
June 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28666265/cap-dependent-translational-control-of-oncolytic-measles-virus-infection-in-malignant-mesothelioma
#20
Blake A Jacobson, Ahad A Sadiq, Shaogeng Tang, Joe Jay-Dixon, Manish R Patel, Jeremy Drees, Brent S Sorenson, Stephen J Russell, Robert A Kratzke
Malignant mesothelioma has a poor prognosis for which there remains an urgent need for successful treatment approaches. Infection with the Edmonston vaccine strain (MV-Edm) derivative of measles virus results in lysis of cancer cells and has been tested in clinical trials for numerous tumor types including mesothelioma. Many factors play a role in MV-Edm tumor cell selectivity and cytopathic activity while also sparing non-cancerous cells. The MV-Edm receptor CD46 (cluster of differentiation 46) was demonstrated to be significantly higher in mesothelioma cells than in control cells...
June 27, 2017: Oncotarget
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