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Oncolytic viral therapy

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https://www.readbyqxmd.com/read/28611307/review-oncolytic-virotherapy-updates-and-future-directions
#1
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
#2
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/28604109/viral-gene-therapy-for-breast-cancer-progress-and-challenges
#3
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/28594388/gene-therapy-for-pancreatic-cancer-specificity-issues-and-hopes
#4
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
#5
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/28589085/immune-system-friend-or-foe-of-oncolytic-virotherapy
#6
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
#7
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/28578991/oncolytic-vsv-primes-differential-responses-to-immuno-oncology-therapy
#8
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/28573184/a-comparative-study-of-replication-incompetent-and-competent-adenoviral-therapy-mediated-immune-response-in-a-murine-glioma-model
#9
Julius W Kim, Jason Miska, Jacob S Young, Aida Rashidi, J Robert Kane, Wojciech K Panek, Deepak Kanojia, Yu Han, Irina V Balyasnikova, Maciej S Lesniak
Oncolytic virotherapy is a treatment approach with increasing clinical relevance, as indicated by the marked survival benefit seen in animal models and its current exploration in human patients with cancer. The use of an adenovirus vector for this therapeutic modality is common, has significant clinical benefit in animals, and its efficacy has recently been linked to an anti-tumor immune response that occurs following tumor antigen presentation. Here, we analyzed the adaptive immune system's response following viral infection by comparing replication-incompetent and replication-competent adenoviral vectors...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28568891/oncolytic-maraba-virus-mg1-as-a-treatment-for-sarcoma
#10
Fabrice Le Boeuf, Mohammed Selman, Hwan Hee Son, Anabel Bergeron, Andrew Chen, Jovian Tsang, Derek Butterwick, Rozanne Arulanandam, Nicole E Forbes, Fanny Tzelepis, John C Bell, Joel Werier, Hesham Abdelbary, Jean-Simon Diallo
The poor prognosis of patients with advanced bone and soft-tissue sarcoma has not changed in the past several decades, highlighting the necessity for new therapeutic approaches. Immunotherapies, including oncolytic viral (OV) therapy, have shown great promise in a number of clinical trials for a variety of tumor types. However, the effective application of OV in treating sarcoma still remains to be demonstrated. Although few pre-clinical studies using distinct OVs have been performed and demonstrated therapeutic benefit in sarcoma models, a side-by-side comparison of clinically relevant OV platforms has not been performed...
May 31, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28567163/targeting-melanoma-with-cancer-killing-viruses
#11
Tiantian Zhang, Yogesh R Suryawanshi, Helene M Woyczesczyk, Karim Essani
Melanoma is the deadliest skin cancer with ever-increasing incidence. Despite the development in diagnostics and therapies, metastatic melanoma is still associated with significant morbidity and mortality. Oncolytic viruses (OVs) represent a class of novel therapeutic agents for cancer by possessing two closely related properties for tumor reduction: virus-induced lysis of tumor cells and induction of host anti-tumor immune responses. A variety of viruses, either in "natural" or in genetically modified forms, have exhibited a remarkable therapeutic efficacy in regressing melanoma in experimental and/or clinical studies...
2017: Open Virology Journal
https://www.readbyqxmd.com/read/28566380/seneca-valley-virus-suppresses-host-type-i-interferon-production-by-targeting-adaptor-proteins-mavs-trif-and-tank-for-cleavage
#12
Suhong Qian, Wenchun Fan, Tingting Liu, Mengge Wu, Huawei Zhang, Xiaofang Cui, Yun Zhou, Junjie Hu, Shaozhong Wei, Huanchun Chen, Xiangmin Li, Ping Qian
Seneca Valley Virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anti-cancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial anti-viral signaling (MAVS), Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF), and TRAF family member-associated NF-κB activator (TANK) via viral 3C(pro) SVV 3C(pro) mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28566376/ruxolitinib-and-polycation-combination-treatment-overcomes-multiple-mechanisms-of-resistance-of-pancreatic-cancer-cells-to-oncolytic-vesicular-stomatitis-virus
#13
Sébastien A Felt, Gaith N Droby, Valery Z Grdzelishvili
Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV). Although VSV is effective against a majority of pancreatic ductal adenocarcinoma (PDAC) cell lines, some PDAC cell lines are highly resistant to VSV, and the mechanisms of the resistance are still unclear. JAK 1/2 inhibitors (such as ruxolitinib and JAK Inhibitor 1) strongly stimulate VSV replication and oncolysis in all resistant cell lines, but only partially improve susceptibility of resistant PDACs to VSV. VSV tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication, rather than on receptor specificity, with several ubiquitously expressed cell-surface molecules to play a role in VSV attachment to host cells...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28561676/the-promise-of-immunotherapy-in-the-treatment-of-hepatocellular-carcinoma
#14
Anthony El-Khoueiry
Advanced hepatocellular carcinoma (HCC) has presented a therapeutic challenge. Despite its heterogeneity, which is partially related to its various etiologies, it frequently arises in a background of chronic inflammation, which makes it a potentially excellent candidate for immunotherapeutic approaches. There is evidence of antitumor immunity in HCC as manifested by the cell infiltrate and its association with prognosis, the presence of tumor-associated antigens, and the reports of immune-mediated spontaneous regressions...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28559846/oncolytic-herpes-simplex-viral-therapy-a-stride-toward-selective-targeting-of-cancer-cells
#15
REVIEW
Dhaval S Sanchala, Lokesh K Bhatt, Kedar S Prabhavalkar
Oncolytic viral therapy, which makes use of replication-competent lytic viruses, has emerged as a promising modality to treat malignancies. It has shown meaningful outcomes in both solid tumor and hematologic malignancies. Advancements during the last decade, mainly genetic engineering of oncolytic viruses have resulted in improved specificity and efficacy of oncolytic viruses in cancer therapeutics. Oncolytic viral therapy for treating cancer with herpes simplex virus-1 has been of particular interest owing to its range of benefits like: (a) large genome and power to infiltrate in the tumor, (b) easy access to manipulation with the flexibility to insert multiple transgenes, (c) infecting majority of the malignant cell types with quick replication in the infected cells and (d) as Anti-HSV agent to terminate HSV replication...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28542292/development-of-a-versatile-oncolytic-virus-platform-for-local-intra-tumoural-expression-of-therapeutic-transgenes
#16
Nalini Marino, Sam Illingworth, Prithvi Kodialbail, Ashvin Patel, Hugo Calderon, Rochelle Lear, Kerry D Fisher, Brian R Champion, Alice C N Brown
Oncolytic viruses which infect and kill tumour cells can also be genetically modified to express therapeutic genes that augment their anti-cancer activities. Modifying oncolytic viruses to produce effective cancer therapies is challenging as encoding transgenes often attenuates virus activity or prevents systemic delivery in patients due to the risk of off-target expression of transgenes in healthy tissues. To overcome these issues we aimed to generate a readily modifiable virus platform using the oncolytic adenovirus, enadenotucirev...
2017: PloS One
https://www.readbyqxmd.com/read/28536354/viroimmunotherapy-for-colorectal-cancer-clinical-studies
#17
REVIEW
Shyambabu Chaurasiya, Susanne Warner
Colorectal cancer is a leading cause of cancer incidence and death. Therapies for those with unresectable or recurrent disease are not considered curative at present. More effective and less toxic therapies are desperately needed. Historically, the immune system was thought to be an enemy to oncolytic viral therapy. Thinking that oncolysis would be the only mechanism for cell death, oncolytic virologists theorized that immune clearance was a detriment to oncolysis. Recent advances in our understanding of the tumor microenvironment, and the interplay of tumor survival and a patient's immune system have called into question our understanding of both arenas...
March 10, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536353/the-continued-promise-and-many-disappointments-of-oncolytic-virotherapy-in-gastrointestinal-malignancies
#18
REVIEW
Daniel H Ahn, Tanios Bekaii-Saab
Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies. Oncolytic viruses, including genetically engineered and naturally occurring viruses, can selectively replicate in and induce tumor cell apoptosis without harming normal tissues, thus offering a promising tool in the armamentarium for cancer therapy. While this approach has garnered much interest over the past several decades, there has not been significant headway across various tumor types. The recent approval of talimogene laherparepvec, a second-generation oncolytic herpes simplex virus type-1, for the treatment of metastatic melanoma, confirms the therapeutic potential of oncolytic viral therapy...
March 4, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536346/taking-a-stab-at-cancer-oncolytic-virus-mediated-anti-cancer-vaccination-strategies
#19
REVIEW
Amelia Sadie Aitken, Dominic Guy Roy, Marie-Claude Bourgeois-Daigneault
Vaccines have classically been used for disease prevention. Modern clinical vaccines are continuously being developed for both traditional use as well as for new applications. Typically thought of in terms of infectious disease control, vaccination approaches can alternatively be adapted as a cancer therapy. Vaccines targeting cancer antigens can be used to induce anti-tumour immunity and have demonstrated therapeutic efficacy both pre-clinically and clinically. Various approaches now exist and further establish the tremendous potential and adaptability of anti-cancer vaccination...
January 4, 2017: Biomedicines
https://www.readbyqxmd.com/read/28525366/mesenchymal-stem-cell-carriers-enhance-antitumor-efficacy-of-oncolytic-adenoviruses-in-an-immunocompetent-mouse-model
#20
Esther Rincón, Teresa Cejalvo, Deepak Kanojia, Arantzazu Alfranca, Miguel Ángel Rodríguez-Milla, Raul Andrés Gil Hoyos, Yu Han, Lingjiao Zhang, Ramón Alemany, Maciej S Lesniak, Javier García-Castro
Oncolytic virotherapy represents a promising alternative for cancer treatment; however, viral delivery to the tumor represents a major challenge. Mesenchymal stem cells (MSCs) chemotax to tumors, and can serve as a viral delivery tool. Previously, we demonstrated antitumor therapeutic efficacy for mesenchymal stem cells (MSCs) infected with the oncolytic human adenovirus ICOVIR5 (Celyvir) for treatment of neuroblastoma patients. Given the lack of suitable immunocompetent preclinical models, the mechanism underlying Celyvir antitumor activity remains unknown...
May 2, 2017: Oncotarget
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