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Oncolytic viral therapy

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https://www.readbyqxmd.com/read/27902444/oncolytic-reovirus-as-a-combined-antiviral-and-anti-tumour-agent-for-the-treatment-of-liver-cancer
#1
Adel Samson, Matthew J Bentham, Karen Scott, Gerard Nuovo, Abigail Bloy, Elizabeth Appleton, Robert A Adair, Rajiv Dave, Adam Peckham-Cooper, Giles Toogood, Seishi Nagamori, Matthew Coffey, Richard Vile, Kevin Harrington, Peter Selby, Fiona Errington-Mais, Alan Melcher, Stephen Griffin
OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. DESIGN AND RESULTS: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication...
November 15, 2016: Gut
https://www.readbyqxmd.com/read/27901484/gene-expression-profiling-of-hematologic-malignant-cell-lines-resistant-to-oncolytic-virus-treatment
#2
Nam Hee Lee, Mikyung Kim, Sung Yong Oh, Seong-Geun Kim, Hyuk-Chan Kwon, Tae-Ho Hwang
Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virotherapy. Pexa-Vec demonstrates oncolytic and immunotherapeutic mechanisms of action. But the determinants of resistance to Pexa-Vec are mostly unknown. We treated hemoatologic malignant cells with Pexa-Vec and examined the gene-expression pattern of sensitive and resistant cells. Human myeloid malignant cell lines (RPMI-8226, IM-9, K562, THP-1) and lymphoid cancer cell lines (MOLT4, CCRF-CEM, Ramos, U937) were treated with Pexa-Vec...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901098/tumor-specific-delivery-of-biologics-by-a-novel-t-cell-line-hozot
#3
Teppei Onishi, Hiroshi Tazawa, Yuuri Hashimoto, Makoto Takeuchi, Takeshi Otani, Shuji Nakamura, Fuminori Sakurai, Hiroyuki Mizuguchi, Hiroyuki Kishimoto, Yuzo Umeda, Yasuhiro Shirakawa, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
"Cell-in-cell" denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896219/enhanced-therapeutic-efficacy-in-cancer-patients-by-short-term-fasting-the-autophagy-connection
#4
REVIEW
Gustav van Niekerk, Suzèl M Hattingh, Anna-Mart Engelbrecht
Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27861142/newcastle-disease-virus-employs-macropinocytosis-and-rab5a-dependent-intracellular-trafficking-to-infect-df-1-cells
#5
Lei Tan, Yuqiang Zhang, Yuan Zhan, Yanmei Yuan, Yingjie Sun, Xusheng Qiu, Chunchun Meng, Cuiping Song, Ying Liao, Chan Ding
Oncolytic Newcastle disease virus (NDV) reportedly employs direct fusion of the viral envelope with the plasma membrane and caveolae-dependent endocytosis to enter cells. Here, we show that macropinocytosis and clathrin-mediated endocytosis are involved in NDV entry into a galline embryonic fibroblast cell line. Upon specific inhibition of clathrin assembly, GTPase dynamin, Na+/H+ exchangers, Ras-related C3 botulinum toxin substrate 1, p21 activated kinase 1 or protein kinase C, entry of NDV and its propagation were suppressed...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27852701/bai1-orchestrates-macrophage-inflammatory-response-to-hsv-infection-implications-for-oncolytic-viral-therapy
#6
Chelsea M Bolyard, Walter Hans Meisen, Yeshavanth Banasavadi-Siddegowda, Jayson Hardcastle, Ji Young Yoo, Eric S Wohleb, Jeffrey Wojton, Jun-Ge Yu, Samuel Dubin, Maninder Khosla, Bo Xu, Jonathon G Smith, Christopher Alvarez-Breckenridge, Pete Pow-Anpongkul, Flavia Pichiorri, Jianying Zhang, Matthew Old, Dan Zhu, Erwin G Van Meir, Jonathan Godbout, Michael A Caligiuri, Jianhua Yu, Balveen Kaur
PURPOSE: Brain Angiogenesis Inhibitor (BAI1) facilitates phagocytosis, and bacterial pathogen clearance by macrophages; however, its role in viral infections is unknown. Here we examined the role of BAI1, and its N-terminal cleavage fragment (Vstat120) in antiviral macrophage responses to oncolytic herpes simplex virus (oHSV). EXPERIMENTAL DESIGN: Changes in infiltration and activation of monocytic and microglial cells after treatment of glioma-bearing mice brains with a control (rHSVQ1) or Vstat120-expressing (RAMBO) oHSV was analyzed using flow cytometry...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27847360/parvovirus-capsid-structures-required-for-infection-mutations-controlling-receptor-recognition-and-protease-cleavages
#7
Heather M Callaway, Kurtis H Feng, Donald W Lee, Andrew B Allison, Melissa Pinard, Robert McKenna, Mavis Agbandje-McKenna, Susan Hafenstein, Colin R Parrish
: Parvovirus capsids are small but complex molecular machines responsible for undertaking many of the steps of cell infection, genome packing, and cell-to-cell as well as host-to-host transfer. The details of parvovirus infection of cells are still not fully understood, but the processes must involve small changes in the capsid structure that allow the endocytosed virus to escape from the endosome, pass through the cell cytoplasm, and deliver the ssDNA genome to the nucleus where viral replication occurs...
November 9, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27806313/recombinant-oncolytic-poliovirus-pvsripo-has-potent-cytotoxic-and-innate-inflammatory-effects-mediating-therapy-in-human-breast-and-prostate-cancer-xenograft-models
#8
Eda K Holl, Michael C Brown, David Boczkowski, Megan A McNamara, Daniel J George, Darell D Bigner, Matthias Gromeier, Smita K Nair
Intratumoral inoculation of viruses with tumor-selective cytotoxicity may induce cancer cell death and, thereby, shrink neoplastic lesions. It is unlikely, however, that viral tumor cell killing alone could produce meaningful, durable clinical responses, as clinically suitable 'oncolytic' viruses are severely attenuated and their spread and propagation are opposed by host immunity. Thus, a more propitious event in this context is the innate antiviral response to intratumoral virus administration, in particular for recruiting durable adaptive immune effector responses...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27805805/mild-hyperthermia-induced-by-gold-nanorod-mediated-plasmonic-photothermal-therapy-enhances-transduction-and-replication-of-oncolytic-adenoviral-gene-delivery
#9
Bo-Kyeong Jung, Yeon Kyung Lee, Jinwoo Hong, Hamidreza Ghandehari, Chae-Ok Yun
Oncolytic adenovirus (Ad) is a promising candidate for cancer gene therapy. However, as a monotherapy it has shown insufficient therapeutic efficacy in clinical trials. In this work we demonstrate that gold nanorod (GNR)-mediated mild hyperthermia enhances the cellular uptake and consequent gene expression of oncolytic Ad to head and neck tumor cells. We examined the combination of oncolytic Ad expressing vascular endothelial growth factor (VEGF) promoter-targeted artificial transcriptional repressor zinc-finger protein and GNR-mediated mild hyperthermia to improve antitumor effect...
November 2, 2016: ACS Nano
https://www.readbyqxmd.com/read/27783991/oncolytic-vaccinia-virus-combined-with-radiotherapy-induces-apoptotic-cell-death-in-sarcoma-cells-by-down-regulating-the-inhibitors-of-apoptosis
#10
Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27767087/adenovirus-coxsackie-adenovirus-receptor-mediated-binding-to-human-erythrocytes-does-not-preclude-systemic-transduction
#11
L A Rojas, R Moreno, H Calderón, R Alemany
There is great skepticism in the capability of adenovirus vectors and oncolytic adenoviruses to reach specific organs or tumors upon systemic administration. Besides antibodies, the presence of CAR (coxsackie and adenovirus receptor) in human erythrocytes has been postulated to sequester CAR-binding adenoviruses, commonly used in gene therapy and oncolytic applications. The use of non-CAR-binding fibers or serotypes has been postulated to solve this limitation. Given the lack of integrins in erythrocytes and therefore of internalization of the CAR-bound virus, we hypothesized that the interaction of adenovirus type 5 (Ad5) with CAR in human erythrocytes could be reversible...
October 21, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27760834/enhanced-oncolytic-activities-of-the-telomerase-specific-replication-competent-adenovirus-expressing-short-hairpin-rna-against-dicer
#12
Mitsuhiro Machitani, Fuminori Sakurai, Keisaku Wakabayashi, Masashi Tachibana, Toshiyoshi Fujiwara, Hiroyuki Mizuguchi
Oncolytic viruses have been receiving much attention as potential agents for cancer treatment. Among the various types of oncolytic viruses, the telomerase-specific replication-competent adenovirus (TRAD), which carries the tumor-specific promoter-driven E1 gene expression cassette, exhibits efficient antitumor effects. The development of a novel TRAD that shows higher replication efficiency and antitumor activity would be highly beneficial for safer and more efficient cancer therapy. We recently demonstrated that the endoribonuclease Dicer significantly inhibits the replication of wild-type adenovirus (Ad) via the processing of viral-associated (VA)-RNAs, which are Ad-encoded small noncoding RNAs, and that the knockdown of Dicer leads to enhanced VA-RNA expression and Ad replication after infection with wild-type Ad...
October 19, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27738655/application-of-interferon-modulators-to-overcome-partial-resistance-of-human-ovarian-cancers-to-vsv-gp-oncolytic-viral-therapy
#13
Catherine Dold, Carles Rodriguez Urbiola, Guido Wollmann, Lisa Egerer, Alexander Muik, Lydia Bellmann, Heidelinde Fiegl, Christian Marth, Janine Kimpel, Dorothee von Laer
Previously, we described an oncolytic vesicular stomatitis virus variant pseudotyped with the nonneurotropic glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, which was highly effective in glioblastoma. Here, we tested its potency for the treatment of ovarian cancer, a leading cause of death from gynecological malignancies. Effective oncolytic activity of VSV-GP could be demonstrated in ovarian cancer cell lines and xenografts in mice; however, remission was temporary in most mice. Analysis of the innate immune response revealed that ovarian cancer cell lines were able to respond to and produce type I interferon, inducing an antiviral state upon virus infection...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27708236/engineering-of-double-recombinant-vaccinia-virus-with-enhanced-oncolytic-potential-for-solid-tumor-virotherapy
#14
Galina Kochneva, Galina Sivolobova, Anastasiya Tkacheva, Antonina Grazhdantseva, Olga Troitskaya, Anna Nushtaeva, Anastasiya Tkachenko, Elena Kuligina, Vladimir Richter, Olga Koval
Vaccinia virus (VACV) oncolytic therapy has been successful in a number of tumor models. In this study our goal was to generate a double recombinant vaccinia virus (VV-GMCSF-Lact) with enhanced antitumor activity that expresses exogenous proteins: the antitumor protein lactaptin and human granulocyte-macrophage colony-stimulating factor (GM-CSF). Lactaptin has previously been demonstrated to act as a tumor suppressor in mouse hepatoma as well as MDA-MB-231 human adenocarcinoma cells grafted into SCID mice. VV-GMCSF-Lact was engineered from Lister strain (L-IVP) vaccinia virus and has deletions of the viral thymidine kinase and vaccinia growth factor genes...
September 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27660707/into-the-clinic-talimogene-laherparepvec-t-vec-a-first-in-class-intratumoral-oncolytic-viral-therapy
#15
Hasan Rehman, Ann W Silk, Michael P Kane, Howard L Kaufman
With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27635234/virotherapy-cancer-gene-therapy-at-last
#16
REVIEW
Alan E Bilsland, Pavlina Spiliopoulou, T R Jeffry Evans
For decades, effective cancer gene therapy has been a tantalising prospect; for a therapeutic modality potentially able to elicit highly effective and selective responses, definitive efficacy outcomes have often seemed out of reach. However, steady progress in vector development and accumulated experience from previous clinical studies has finally led the field to its first licensed therapy. Following a pivotal phase III trial, Imlygic (talimogene laherparepvec/T-Vec) received US approval as a treatment for cutaneous and subcutaneous melanoma in October 2015, followed several weeks later by its European authorisation...
2016: F1000Research
https://www.readbyqxmd.com/read/27635026/enhancing-expression-of-functional-human-sodium-iodide-symporter-and-somatostatin-receptor-in-recombinant-oncolytic-vaccinia-virus-for-in-vivo-imaging-of-tumors
#17
Jiahu Wang, Rozanne Arulanandam, Richard Wassenaar, Theresa Falls, Julia Petryk, Judith Paget, Kenneth Garson, Catia Cemeus, Barbara Vanderhyden, Glenn Wells, John Bell, Fabrice Le Boeuf
PURPOSE: Oncolytic virus (OV) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. As a live biological agent, oncolytic virus has the ability to target and selectively amplify at the tumor sites. We have reported that a vaccinia-based OV (Pexa-Vec) has shown good efficacy in pre-clinical models and in clinical trials. In order to give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral based platforms with two specific gene reporters...
September 15, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27622605/lentivirus-mediated-p21-waf-1-short-hairpin-rna-enhances-the-cytotoxic-effects-and-replicative-potential-of-a-bladder-cancer-specific-oncolytic-adenovirus-in-vitro
#18
Jie Shi, Shengjun Fu, Li Wang, Yan Tao, Ronald Rodriguez, Zhiping Wang
Our previous work confirmed that the bladder cancer-specific oncolytic adenovirus Ad/PSCAE/UPII/E1A could selectively replicate in bladder cancer cells, thus causing specific tumor cell lysis. The replicative potential is a crucial factor in determining the therapeutic efficacy of oncolytic adenoviruses. However, viral replication is attenuated by the low-activity promoter that we used, thus compromising viral cytotoxicity. In this study, we investigated the effect of the cell cycle-dependent kinase inhibitor p21/Waf-1 on an adenovirus...
January 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27594905/role-of-nanotechnology-and-gene-delivery-systems-in-trail-based-therapies
#19
REVIEW
George E Naoum, Fady Tawadros, Ammad Ahmad Farooqi, Muhammad Zahid Qureshi, Sobia Tabassum, Donald J Buchsbaum, Waleed Arafat
Since its identification as a member of the tumour necrosis factor (TNF) family, TRAIL (TNF-related apoptosis-inducing ligand) has emerged as a new avenue in apoptosis-inducing cancer therapies. Its ability to circumvent the chemoresistance of conventional therapeutics and to interact with cancer stem cells (CSCs) self-renewal pathways, amplified its potential as a cancer apoptotic agent. Many recombinant preparations of this death ligand and monoclonal antibodies targeting its death receptors have been tested in monotherapy and combinational clinical trials...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27593990/towards-targeted-cancer-therapy-aptamer-or-oncolytic-virus
#20
Kei X Tan, Michael K Danquah, Amandeep Sidhu, Clarence M Ongkudon, Sie Yon Lau
Cancer is a leading cause of global mortality. Whilst anticancer awareness programs have increased significantly over the years, scientific research into the development of efficient and specific drugs to target cancerous cells for enhanced therapeutic effects has not received much clinical success. Chemotherapeutic agents are incapable of acting specifically on cancerous cells, thus causing low therapeutic effects accompanied by toxicity to surrounding normal tissues. The search for smart, highly specific and efficient cancer treatments and delivery systems continues to be a significant research endeavor...
September 1, 2016: European Journal of Pharmaceutical Sciences
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