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Oncolytic viruses

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https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#1
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27902444/oncolytic-reovirus-as-a-combined-antiviral-and-anti-tumour-agent-for-the-treatment-of-liver-cancer
#2
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/27902314/newcastle-disease-virus-degrades-hif-1%C3%AE-through-proteasomal-pathways-independent-of-vhl-and-p53
#3
Noraini Abd-Aziz, Eric Stanbridge, Norazizah Shafee
Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated alpha (HIF-1α) and a constitutive beta subunit (HIF-1β)...
October 6, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901484/gene-expression-profiling-of-hematologic-malignant-cell-lines-resistant-to-oncolytic-virus-treatment
#4
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
#5
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
#6
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/27879135/the-role-of-tnf-%C3%AE-inhibitor-in-glioma-virotherapy-a-mathematical-model
#7
Elzbieta Ratajczyk, Urszula Ledzewicz, Maciej Leszczynski, Avner Friedman
Virotherapy, using herpes simplex virus, represents a promising therapy of glioma. But the innate immune response, which includes TNF-α produced by macrophages, reduces the effectiveness of the treatment. Hence treatment with TNF-α inhibitor may increase the effectiveness of the virotherapy. In the present paper we develop a mathematical model that includes continuous infusion of the virus in combination with TNF-α inhibitor. We study the efficacy of the treatment under different combinations of the two drugs for different scenarios of the burst size of newly formed virus emerging from dying infected cancer cells...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27875627/immunotherapy-approaches-in-the-treatment-of-malignant-brain-tumors
#8
REVIEW
Anastasie M Dunn-Pirio, Gordana Vlahovic
Glioblastoma is the most common malignant primary brain tumor. Despite standard-of-care treatment, consisting of maximal surgical resection followed by chemoradiation, both morbidity and mortality associated with this disease remain very poor. Therefore, there is an urgent need for more efficacious and well tolerated therapies. Advancing knowledge of the intricate interplay between malignant gliomas and the immune system, coupled with the recent launch of immunotherapy research for other cancers, has led to a veritable increase in immunotherapy investigation for glioblastoma and other malignant gliomas...
November 22, 2016: Cancer
https://www.readbyqxmd.com/read/27867771/prospect-and-progress-of-oncolytic-viruses-for-treating-peripheral-nerve-sheath-tumors
#9
Slawomir Antoszczyk, Samuel D Rabkin
INTRODUCTION: Peripheral nerve sheath tumors (PNSTs) are an assorted group of neoplasms originating from neuroectoderm and growing in peripheral nerves. Malignant transformation leads to a poor prognosis and is often lethal. Current treatment of PNSTs is predominantly surgical, which is often incomplete or accompanied by significant loss of function, in conjunction with radiotherapy and/or chemotherapy, for which the benefits are inconclusive. Oncolytic viruses (OVs) efficiently kill tumor cells while remaining safe for normal tissues, and are a novel antitumor therapy for patients with PNSTs...
2016: Expert Opinion on Orphan Drugs
https://www.readbyqxmd.com/read/27865863/curcumin-promotes-the-oncoltyic-capacity-of-vesicular-stomatitis-virus-for-the-treatment-of-prostate-cancers
#10
Dylan J Fehl, Maryam Ahmed
Vesicular stomatitis virus (VSV) matrix (M) protein mutants have been studied as oncolytic agents due to their capacity to effectively kill cancer cells while exhibiting low virulence in vivo. Despite encouraging results, many cancer cells maintain resistance to oncolytic VSV mutants in part due to residual antiviral responses. We sought to determine whether combination of VSV with natural agents with anti-tumor properties, such as curcumin, resveratrol, and flavokavain B, would enhance tumor cell killing in a prostate cancer model...
November 16, 2016: Virus Research
https://www.readbyqxmd.com/read/27861142/newcastle-disease-virus-employs-macropinocytosis-and-rab5a-dependent-intracellular-trafficking-to-infect-df-1-cells
#11
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/27860224/reduced-angiogenic-gene-expression-in-morbillivirus-triggered-oncolysis-in-a-translational-model-for-histiocytic-sarcoma
#12
Vanessa Maria Pfankuche, Ingo Spitzbarth, Stefanie Lapp, Reiner Ulrich, Ulrich Deschl, Arno Kalkuhl, Wolfgang Baumgärtner, Christina Puff
Histiocytic sarcoma represents a rare malignant tumour with a short survival time, indicating the need of novel treatment strategies including oncolytic virotherapy. The underlying molecular mechanisms of viral oncolysis are largely unknown. As cancer in companion animals shares striking similarities with human counterparts, we chose a permanent canine histiocytic sarcoma cell line (DH82 cells) to identify global transcriptome changes following infection with canine distemper virus (CDV), a paramyxovirus closely related to human measles virus...
November 17, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27859242/meeting-report-4-th-european-seminars-in-virology-on-oncogenic-and-oncolytic-viruses-in-bertinoro-bologna-italy
#13
Alberto Reale, Lorenzo Messa, Adriana Vitiello, Arianna Loregian, Giorgio Palù
The 4(th) European Seminars in Virology (EuSeV), which was focused on oncogenic and oncolytic viruses, was held in Bertinoro (Bologna), Italy, from June 10 to 12, 2016. This article summarizes the plenary lectures and aims to illustrate the main topics discussed at 4(th) EuSeV, which brought together knowledge and expertise in the field of oncogenic and oncolytic viruses from all over the world. The meeting was divided in two parts, "Mechanisms of Viral Oncogenesis" and "Viral Oncolysis and Immunotherapy", which were both focused on dissecting the complex and multi-factorial interplay between cancer and human viruses and on exploring new anti-cancer strategies...
November 16, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27853644/vectorization-in-an-oncolytic-vaccinia-virus-of-an-antibody-a-fab-and-a-scfv-against-programmed-cell-death-1-pd-1-allows-their-intratumoral-delivery-and-an-improved-tumor-growth-inhibition
#14
Patricia Kleinpeter, Laetitia Fend, Christine Thioudellet, Michel Geist, Nathalie Sfrontato, Véronique Koerper, Catherine Fahrner, Doris Schmitt, Murielle Gantzer, Christelle Remy-Ziller, Renée Brandely, Dominique Villeval, Karola Rittner, Nathalie Silvestre, Philippe Erbs, Laurence Zitvogel, Eric Quéméneur, Xavier Préville, Jean-Baptiste Marchand
We report here the successful vectorization of a hamster monoclonal IgG (namely J43) recognizing the murine Programmed cell death-1 (mPD-1) in Western Reserve (WR) oncolytic vaccinia virus. Three forms of mPD-1 binders have been inserted into the virus: whole antibody (mAb), Fragment antigen-binding (Fab) or single-chain variable fragment (scFv). MAb, Fab and scFv were produced and assembled with the expected patterns in supernatants of cells infected by the recombinant viruses. The three purified mPD-1 binders were able to block the binding of mPD-1 ligand to mPD-1 in vitro...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27852701/bai1-orchestrates-macrophage-inflammatory-response-to-hsv-infection-implications-for-oncolytic-viral-therapy
#15
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/27847861/a-novel-polymer-coated-oncolytic-measles-virus-overcomes-immune-suppression-and-induces-robust-antitumor-activity
#16
Kaname Nosaki, Katsuyuki Hamada, Yuto Takashima, Miyako Sagara, Yumiko Matsumura, Shohei Miyamoto, Yasuki Hijikata, Toshihiko Okazaki, Yoichi Nakanishi, Kenzaburo Tani
Although various therapies are available to treat cancers, including surgery, chemotherapy, and radiotherapy, cancer has been the leading cause of death in Japan for the last 30 years, and new therapeutic modalities are urgently needed. As a new modality, there has recently been great interest in oncolytic virotherapy, with measles virus being a candidate virus expected to show strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the host immune response in previous clinical trials...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27847360/parvovirus-capsid-structures-required-for-infection-mutations-controlling-receptor-recognition-and-protease-cleavages
#17
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/27827454/novel-high-throughput-approach-for-purification-of-infectious-virions
#18
Kevin T James, Brad Cooney, Kate Agopsowicz, Mary Ann Trevors, Adil Mohamed, Don Stoltz, Mary Hitt, Maya Shmulevitz
Viruses are extensively studied as pathogens and exploited as molecular tools and therapeutic agents. Existing methods to purify viruses such as gradient ultracentrifugation or chromatography have limitations, for example demand for technical expertise or specialized equipment, high time consumption, and restricted capacity. Our laboratory explores mutations in oncolytic reovirus that could improve oncolytic activity, and makes routine use of numerous virus variants, genome reassortants, and reverse engineered mutants...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27825920/a-generic-viral-dynamic-model-to-systematically-characterize-the-interaction-between-oncolytic-virus-kinetics-and-tumor-growth
#19
Melanie I Titze, Julia Frank, Michael Ehrhardt, Sigrun Smola, Norbert Graf, Thorsten Lehr
Oncolytic viruses (OV) represent an encouraging new therapeutic concept for treatment of human cancers. OVs specifically replicate in tumor cells and initiate cell lysis whilst tumor cells act as endogenous bioreactors for virus amplification. This complex bidirectional interaction between tumor and oncolytic virus hampers the establishment of a straight dose-concentration-effect relation. We aimed to develop a generic mathematical pharmacokinetic/pharmacodynamics (PK/PD) model to characterize the relationship between tumor cell growth and kinetics of different OVs...
November 5, 2016: European Journal of Pharmaceutical Sciences
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
#20
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
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