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Oncolytic viruses

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https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#1
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634751/herpesviral-vectors-and-their-application-in-oncolytic-therapy-vaccination-and-gene-transfer
#2
REVIEW
Susanne M Bailer, Christina Funk, André Riedl, Zsolt Ruzsics
Herpesviruses are enveloped DNA viruses that infect vertebrate cells. Their high potential cloning capacity and the lifelong persistence of their genomes in various host cells make them attractive platforms for vector-based therapy. In this review, we would like to highlight recent advances of three major areas of herpesvirus vector development and application: (i) oncolytic therapy, (ii) recombinant vaccines, and (iii) large capacity gene transfer vehicles.
June 20, 2017: Virus Genes
https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#3
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28634161/oncolytic-adenovirus-expressing-bispecific-antibody-targets-t-cell-cytotoxicity-in-cancer-biopsies
#4
Joshua D Freedman, Joachim Hagel, Eleanor M Scott, Ioannis Psallidas, Avinash Gupta, Laura Spiers, Paul Miller, Nikolaos Kanellakis, Rebecca Ashfield, Kerry D Fisher, Margaret R Duffy, Leonard W Seymour
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single-chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T-cell engager (BiTE) binds to EpCAM on target cells and cross-links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication...
June 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28620128/cd133-targeted-oncolytic-adenovirus-demonstrates-anti-tumor-effect-in-colorectal-cancer
#5
Mizuho Sato-Dahlman, Yoshiaki Miura, Jing Li Huang, Praveensingh Hajeri, Kari Jacobsen, Julia Davydova, Masato Yamamoto
Oncolytic Adenoviruses (OAds) are one of the most promising anti-cancer agents that can induce cancer specific cell death. Recently, we generated infectivity-selective OAd, and the resultant OAd tumor-specific binding shows strong efficacy and mitigates toxicity. In this study, we applied this strategy based on adenovirus library screening system for generation of CD133-targeted OAd, and examined their oncolytic activity against colorectal cancer (CRC) in vitro and in vivo. CD133 (Prominin-1) is an important cell surface marker of cancer stem (like) cells (CSCs) in various cancers, including CRC...
June 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611307/review-oncolytic-virotherapy-updates-and-future-directions
#6
REVIEW
Christos Fountzilas, Sukeshi Patel, Devalingam Mahalingam
Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or non-resectable melanoma...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28607950/chemovirotherapy-of-pancreatic-adenocarcinoma-by-combining-oncolytic-vaccinia-virus-glv-1h68-with-nab-paclitaxel-plus-gemcitabine
#7
Eike Binz, Susanne Berchtold, Julia Beil, Martina Schell, Christine Geisler, Irina Smirnow, Ulrich M Lauer
Oncolytic viruses have proven their therapeutic potential against a variety of different tumor entities both in vitro and in vivo. Their ability to selectively infect and lyse tumor cells, while sparing healthy tissues, makes them favorable agents for tumor-specific treatment approaches. Particularly, the addition of virotherapeutics to already established chemotherapy protocols (so-called chemovirotherapy) is of major interest. Here we investigated the in vitro cytotoxic effect of the oncolytic vaccinia virus GLV-1h68 combined with dual chemotherapy with nab-paclitaxel plus gemcitabine in four human pancreatic adenocarcinoma cell lines (AsPc-1, BxPc-3, MIA-PaCa-2, and Panc-1)...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28607091/selective-replication-of-oncolytic-virus-m1-results-in-a-bystander-killing-effect-that-is-potentiated-by-smac-mimetics
#8
Jing Cai, Yuan Lin, Haipeng Zhang, Jiankai Liang, Yaqian Tan, Webster K Cavenee, Guangmei Yan
Oncolytic virotherapy is a treatment modality that uses native or genetically modified viruses that selectively replicate in and kill tumor cells. Viruses represent a type of pathogen-associated molecular pattern and thereby induce the up-regulation of dozens of cytokines via activating the host innate immune system. Second mitochondria-derived activator of caspases (Smac) mimetic compounds (SMCs), which antagonize the function of inhibitor of apoptosis proteins (IAPs) and induce apoptosis, sensitize tumor cells to multiple cytokines...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28604109/viral-gene-therapy-for-breast-cancer-progress-and-challenges
#9
Antonela S Asad, Mariela A Moreno Ayala, M Florencia Gottardo, Camila Zuccato, Alejandro Javier Nicola Candia, Flavia A Zanetti, Adriana Seilicovich, Marianela Candolfi
Breast cancer is the most common cancer in women all over the world. Furthermore, up to one third of breast tumors develop metastases that are resistant to standard therapies. Gene therapeutic strategies have been developed in order to specifically target cancer cells either directly or through the stimulation of antitumor immunity. Areas covered: This review describes the therapeutic strategies that are currently under development to treat this disease using engineered viral vectors including: adenovirus, adeno-associated virus, lentivirus, poxvirus, reovirus, baculovirus, herpesvirus and oncolytic viruses...
June 12, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28599488/histone-deacetylase-inhibitor-trichostatin-a-enhances-the-antitumor-effect-of-the-oncolytic-adenovirus-h101-on-esophageal-squamous-cell-carcinoma-in-vitro-and-in-vivo
#10
Junfen Ma, Nan Li, Jimin Zhao, Jing Lu, Yanqiu Ma, Qinghua Zhu, Ziming Dong, Kangdong Liu, Liang Ming
Replication-selective oncolytic virotherapy provides a novel modality to treat cancer by inducing cell death in tumor cells but not in normal cells. However, the utilization of oncolytic viruses as a stand-alone treatment is problematic due to their poor transduction efficiency in vivo. H101 was the first oncolytic adenovirus (Ads) to be approved by the Chinese FDA, and exhibits modest antitumor effects when applied as a single agent. The multiple histone deacetylase inhibitor trichostatin A (TSA) has been demonstrated to potently enhance the spread and replication of oncolytic Ads in several infection-resistant types of cancer...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28594388/gene-therapy-for-pancreatic-cancer-specificity-issues-and-hopes
#11
REVIEW
Marie Rouanet, Marine Lebrin, Fabian Gross, Barbara Bournet, Pierre Cordelier, Louis Buscail
A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes)...
June 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28593604/neutralization-of-matrix-metalloproteinase-9-potentially-enhances-oncolytic-efficacy-of-tanapox-virus-for-melanoma-therapy
#12
Tiantian Zhang, Yogesh R Suryawanshi, Blair R Szymczyna, Karim Essani
Matrix metalloproteinases (MMPs), which are involved in degradation of extracellular matrix, are critical regulators in tumor progression, metastasis and angiogenesis. Although induction of MMPs is frequently observed during the viral infection, the effect of MMPs on viral replication varies between viruses. MMP-9, for instance, is upregulated and promotes the replication of some viruses, such as herpes simplex virus, but inhibits the replication of others. Here, we report that infection with tanapox virus (TPV) promotes the expression of MMP-9 in the melanoma cells...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28593497/mathematical-and-computational-modeling-for-tumor-virotherapy-with-mediated-immunity
#13
Asim Timalsina, Jianjun Paul Tian, Jin Wang
We propose a new mathematical modeling framework based on partial differential equations to study tumor virotherapy with mediated immunity. The model incorporates both innate and adaptive immune responses and represents the complex interaction among tumor cells, oncolytic viruses, and immune systems on a domain with a moving boundary. Using carefully designed computational methods, we conduct extensive numerical simulation to the model. The results allow us to examine tumor development under a wide range of settings and provide insight into several important aspects of the virotherapy, including the dependence of the efficacy on a few key parameters and the delay in the adaptive immunity...
June 7, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28592535/newcastle-disease-virus-establishes-persistent-infection-in-tumor-cells-in-vitro-contribution-of-the-cleavage-site-of-fusion-protein-and-second-sialic-acid-binding-site-of-hemagglutinin-neuraminidase
#14
Udaya S Rangaswamy, Weijia Wang, Xing Cheng, Patrick McTamney, Danielle Carroll, Hong Jin
Newcastle Disease Virus (NDV) is an oncolytic virus being developed for the treatment of cancer. Following infection of an ovarian human cancer cell line (OVCAR3) with a recombinant low pathogenic NDV, persistent infection (PI) was established in a subset of tumor cells. PI cells exhibited resistance to superinfection with NDV, and an anti-viral state as demonstrated by upregulation of interferon and interferon induced genes such as Myxoma resistance gene 1 (Mx1) and Retinoic acid-inducing gene-I (RIG-I). Viruses released from PI cells induced higher cell to cell fusion following infection compared to the parental virus in two tumor cell lines tested, HT1080 and HeLa, and remained to be attenuated in chickens...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28591723/rip1-is-a-central-signaling-protein-in-regulation-of-tnf-%C3%AE-trail-mediated-apoptosis-and-necroptosis-during-newcastle-disease-virus-infection
#15
Ying Liao, Huaxia Wang, Xiang Mao, Hongjie Fang, Huang Wang, Yanrong Li, Yinjie Sun, Chun Meng, Lei Tan, Cuiping Song, Xusheng Qiu, Chan Ding
Newcastle disease virus (NDV) is an oncolytic virus which selectively replicates in tumor cells and exerts anti-tumor cytotoxic activity by promoting cell death. In this study, we focus on characterization of the underlying mechanisms of NDV-induced cell death in HeLa cells. We find that NDV Herts/33 strain triggers both extrinsic and intrinsic apoptosis at late infection times. The activation of NF-кB pathway and subsequent up-regulation of TNF-α/TRAIL initiates extrinsic apoptosis, leading to activation of caspase 8 and cleavage of Bid into tBid...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589085/immune-system-friend-or-foe-of-oncolytic-virotherapy
#16
REVIEW
Anna C Filley, Mahua Dey
Oncolytic viruses (OVs) are an emerging class of targeted anticancer therapies designed to selectively infect, replicate in, and lyse malignant cells without causing harm to normal, healthy tissues. In addition to direct oncolytic activity, OVs have shown dual promise as immunotherapeutic agents. The presence of viral infection and subsequently generated immunogenic tumor cell death trigger innate and adaptive immune responses that mediate further tumor destruction. However, antiviral immune responses can intrinsically limit OV infection, spread, and overall therapeutic efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28589082/genetically-engineered-vaccinia-viruses-as-agents-for-cancer-treatment-imaging-and-transgene-delivery
#17
REVIEW
Dana Haddad
Despite advances in technology, the formidable challenge of treating cancer, especially if advanced, still remains with no significant improvement in survival rates, even with the most common forms of cancer. Oncolytic viral therapies have shown great promise for the treatment of various cancers, with the possible advantages of stronger treatment efficacy compared to conventional therapy due to higher tumor selectivity, and less toxicity. They are able to preferentially and selectively propagate in cancer cells, consequently destroying tumor tissue mainly via cell lysis, while leaving non-cancerous tissues unharmed...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28587298/serotype-specific-killing-of-large-cell-carcinoma-cells-by-reovirus
#18
Emily J Simon, Morgan A Howells, Johnasha D Stuart, Karl W Boehme
Reovirus is under development as a therapeutic for numerous types of cancer. In contrast to other oncolytic viruses, the safety and efficacy of reovirus have not been improved through genetic manipulation. Here, we tested the oncolytic capacity of recombinant strains (rs) of prototype reovirus laboratory strains T1L and T3D (rsT1L and rsT3D, respectively) in a panel of non-small cell lung cancer (NSCLC) cell lines. We found that rsT1L was markedly more cytolytic than rsT3D in the large cell carcinoma cell lines tested, whereas killing of adenocarcinoma cell lines was comparable between rsT1L and rsT3D...
June 6, 2017: Viruses
https://www.readbyqxmd.com/read/28578991/oncolytic-vsv-primes-differential-responses-to-immuno-oncology-therapy
#19
Nicholas M Durham, Kathy Mulgrew, Kelly McGlinchey, Noel R Monks, Hong Ji, Ronald Herbst, JoAnn Suzich, Scott A Hammond, Elizabeth J Kelly
Vesicular stomatitis virus encoding the IFNβ transgene (VSV-IFNβ) is a mediator of potent oncolytic activity and is undergoing clinical evaluation for the treatment of solid tumors. Emerging preclinical and clinical data suggest treatment of tumors with oncolytic viruses may sensitize tumors to checkpoint inhibitors and increase the anti-tumor immune response. New generations of immuno-oncology molecules including T cell agonists are entering clinical development and could be hypothesized to enhance the activity of oncolytic viruses, including VSV-IFNβ...
June 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28578522/evaluation-of-the-oncolytic-potential-of-r2b-mukteshwar-vaccine-strain-of-newcastle-disease-virus-ndv-in-a-colon-cancer-cell-line-sw-620
#20
Kishan K Sharma, Irsadullakhan H Kalyani, Jogeswar Mohapatra, Satish D Patel, Dharmesh R Patel, Priti D Vihol, Abhijit Chatterjee, Dinesh R Patel, Bhavesh Vyas
Virotherapy is emerging as an alternative treatment of cancer. Among the candidate oncolytic viruses (OVs), Newcastle disease virus (NDV) has emerged as a promising non-engineered OV. In the present communication, we explored the oncolytic potential of R2B Mukteshwar strain of NDV using SW-620 colon cancer cells. SW-620 cells were xenografted in nude mice and after evaluation of the safety profile, 1 x 10(7) plaque forming units (PFU) of NDV were inoculated as virotherapeutic agent via the intratumoral (I/T) and intravenous (I/V) route...
June 3, 2017: Archives of Virology
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