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https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#1
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28316007/talimogene-laherparepvec-for-treating-metastatic-melanoma-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#2
REVIEW
Nigel Fleeman, Adrian Bagust, Angela Boland, Sophie Beale, Marty Richardson, Ashma Krishan, Angela Stainthorpe, Ahmed Abdulla, Eleanor Kotas, Lindsay Banks, Miranda Payne
The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Amgen) of talimogene laherparepvec (T-VEC) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article presents a summary of the company's submission of T-VEC, the ERG review and the resulting NICE guidance (TA410), issued in September 2016...
March 18, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28315557/oncolytic-viruses-treatment-and-implications-for-patients-with-gliomas%C3%A2
#3
Cheryl Martin
BACKGROUND: Oncolytic viral therapies are increasingly being explored for the treatment of diverse cancer types, most notably melanoma. However, advances in the treatment of high-grade gliomas, and specifically glioblastoma multiforme (GBM), are the result of novel oncolytic viral therapies. Delta-24-RGD is one such therapy that has demonstrated promising results in phase 1 trials.
. OBJECTIVES: The objective of this article is to provide an overview of Delta-24-RGD, highlighting considerations for nurses in diverse clinical, research, and advanced practice roles...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315430/oncolytic-adenovirus-expressing-relaxin-ydc002-enhances-therapeutic-efficacy-of-gemcitabine-against-pancreatic-cancer
#4
Kyung Hee Jung, Il-Kyu Choi, Hee-Seung Lee, Hong Hua Yan, Mi Kwon Son, Hyo Min Ahn, JinWoo Hong, Chae-Ok Yun, Soon-Sun Hong
Pancreatic cancer is a highly lethal disease for which limited therapeutic options are available. Pancreatic cancer exhibits a pronounced collagen-rich stromal reaction, which induces chemoresistance by inhibiting drug diffusion into the tumor. Complementary treatment with oncolytic virus such as an oncolytic adenovirus expressing relaxin (YDC002) is an innovative treatment option for combating chemoresistant pancreatic cancer. Here, we examined the ability of combined treatment with gemcitabine and YDC002, which degrades extracellular matrix (ECM), to efficiently treat chemoresistant and desmoplastic pancreatic cancer...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28314785/tumor-localized-secretion-of-soluble-pd1-enhances-oncolytic-virotherapy
#5
Mee Y Bartee, Katherine M Dunlap, Eric Bartee
Oncolytic virotherapy represents an attractive option for the treatment of a variety of aggressive or refractory tumors. While this therapy is effective at rapidly debulking directly injected tumor masses, achieving complete eradication of established disease has proven difficult. One method to overcome this challenge is to use oncolytic viruses to induce secondary anti-tumor immune responses. Unfortunately, while the initial induction of these immune responses is typically robust, their subsequent efficacy is often inhibited through a variety of immunoregulatory mechanisms, including the PD1/PDL1 T-cell checkpoint pathway...
March 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28300077/translational-reprogramming-in-tumour-cells-can-generate-oncoselectivity-in-viral-therapies
#6
Eneko Villanueva, Pilar Navarro, Maria Rovira-Rigau, Annarita Sibilio, Raúl Méndez, Cristina Fillat
Systemic treatment of cancer requires tumour-selective therapies that eliminate cancer cells yet preserve healthy tissues from undesired damage. Tumoral transformation is associated with profound effects in translational reprogramming of gene expression, such that tumour-specific translational regulation presents an attractive possibility for generating oncoselective therapies. We recently discovered that mRNA translational control by cytoplasmic polyadenylation element-binding proteins (CPEBs) is reactivated in cancer...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28289079/deletion-of-f4l-ribonucleotide-reductase-in-vaccinia-virus-produces-a-selective-oncolytic-virus-and-promotes-anti-tumor-immunity-with-superior-safety-in-bladder-cancer-models
#7
Kyle G Potts, Chad R Irwin, Nicole A Favis, Desmond B Pink, Krista M Vincent, John D Lewis, Ronald B Moore, Mary M Hitt, David H Evans
Bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. In particular, standard of care for high-grade disease, Bacillus Calmette-Guérin (BCG), fails in 30% of patients. We have generated a novel oncolytic vaccinia virus (VACV) by mutating the F4L gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (RRM2). The F4L-deleted VACVs are highly attenuated in normal tissues, and since cancer cells commonly express elevated RRM2 levels, have tumor-selective replication and cell killing...
March 13, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28287517/microrna-based-regulation-of-picornavirus-tropism
#8
Autumn J Ruiz, Stephen J Russell
Cell-specific restriction of viral replication without concomitant attenuation can benefit vaccine development, gene therapy, oncolytic virotherapy, and understanding the biological properties of viruses. There are several mechanisms for regulating viral tropism, however they tend to be virus class specific and many result in virus attenuation. Additionally, many viruses, including picornaviruses, exhibit size constraints that do not allow for incorporation of large amounts of foreign genetic material required for some targeting methods...
February 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28274139/immune-and-viral-therapies-for-malignant-primary-brain-tumors
#9
Andrew M Gardeck, Jordan Sheehan, Walter C Low
Glioblastoma multiforme (GBM) is a primary brain tumor with great lethality. Current standard of care with surgery, radiation therapy, and chemotherapy are ineffective in curing this disease. Recent advancements in biological therapies show promise in treating brain tumors. Areas covered: This article provides a review of: the peripheral activation of antigen presenting cells such as dendritic cells to stimulate T cells to recognize and destroy tumor cells within the brain; the ex vivo expansion and transfer of dendritic cells, T cells, and engineered T cells expressing chimeric antigen receptors to target cells bearing specific tumor antigens as well as monoclonal antibodies as immune check point inhibitors...
April 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28265902/oncolytic-virotherapy-for-the-treatment-of-malignant-glioma
#10
REVIEW
Paul M Foreman, Gregory K Friedman, Kevin A Cassady, James M Markert
Malignant glioma is the most common primary brain tumor and carries a grim prognosis, with a median survival of just over 14 months. Given the poor outcomes with standard-of-care treatments, novel treatment strategies are needed. The concept of virotherapy for the treatment of malignant tumors dates back more than a century and can be divided into replication-competent oncolytic viruses and replication-deficient viral vectors. Oncolytic viruses are designed to selectively target, infect, and replicate in tumor cells, while sparing surrounding normal brain...
March 6, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28260622/group-b-adenovirus-enadenotucirev-infects-polarised-colorectal-cancer-cells-efficiently-from-the-basolateral-surface-expected-to-be-encountered-during-intravenous-delivery-to-treat-disseminated-cancer
#11
Suet-Lin Chia, Janet Lei, David J P Ferguson, Arthur Dyer, Kerry D Fisher, Leonard W Seymour
Enadenotucirev (EnAd) is a group B oncolytic adenovirus developed for systemic delivery and currently undergoing clinical evaluation for advanced cancer therapy. For differentiated carcinomas, systemic delivery would likely expose virus particles to the basolateral surface of cancer cells rather than the apical surface encountered during natural infection. Here, we compare the ability of EnAd and adenovirus type-5 (Ad5) to infect polarised colorectal carcinoma cells from the apical or basolateral surfaces. Whereas Ad5 infection was more efficient via the apical than basolateral surface, EnAd readily infected cells from either surface...
March 2, 2017: Virology
https://www.readbyqxmd.com/read/28255168/mapping-sites-of-herpes-simplex-virus-type-1-glycoprotein-d-that-permit-insertions-and-impact-gd-and-gb-receptors-usage
#12
Qing Fan, Sarah Kopp, Sarah A Connolly, William J Muller, Richard Longnecker
Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) is one of four glycoproteins essential for HSV entry and cell fusion. The purpose of this study was to determine the plasticity of gD to tolerate insertion or deletion mutations and to construct an oncolytic HSV-1 that utilizes the disialoganglioside GD2 as a HSV-1 entry receptor. We found that the N-terminus of gD tolerates long insertions, whereas residues adjacent to the gD Ig-like V-type core tolerated shorter insertions (up to 15 amino acids), but not greater than 60 amino acids...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28253733/rationale-and-design-of-a-phase-i-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#13
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy; and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor specific tropism and potential efficacy in the treatment of malignant brain tumors...
February 24, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28251973/-exogenous-bacillus-pumilus-rnase-binase-suppresses-the-reproduction-of-reovirus-serotype-1
#14
M A Efimova, R Shah Mahmud, P V Zelenikhin, M I Sabirova, A I Kolpakov, O N Ilinskaya
The experimental study identified the antiviral activity of Bacillus pumilus RNase (binase) against the reovirus of serotype 1/strain Lang. For the first time, it has been found that 50 μg/mL of binase effectively reduced the hemagglutinin and cytocidal activity of reovirus in Vero cell line. The preincubation of the enzyme with reovirus before infection of the cells inhibited the viral replication. To determine the stagedependent effect of reovirus reproduction upon binase inhibition, the infected cells were treated with binase or RNase A at different phases of the infectious cycle...
January 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28251971/-biomarkers-of-prostate-cancer-sensitivity-to-the-sendai-virus
#15
A A Belova, A O Sosnovtseva, A V Lipatova, K M Njushko, N N Volchenko, M M Belyakov, O V Sudalenko, A A Krasheninnikov, P V Shegai, A F Sadritdinova, M S Fedorova, N V Vorobjov, B Y Alekseev, A D Kaprin, A V Kudryavtseva
Metastatic prostate cancer is often associated with either primary or intractable castration-resistant prostate cancer (CRPC), thus justifying the search for entirely new ways of treatment. Oncolytic viruses are able to selectively induce the death of tumor cells without affecting normal cells. A murine Sendai virus has potential to be used as an oncolytic agent. However, tumors vary in their sensitivity to different viruses, prompting us to attempt to identify corresponding biomarkers that reflect the interaction of cancer cells and the virus...
January 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28250896/endoscopy-guided-ablation-of-pancreatic-lesions-technical-possibilities-and-clinical-outlook
#16
REVIEW
Marianna Signoretti, Roberto Valente, Alessandro Repici, Gianfranco Delle Fave, Gabriele Capurso, Silvia Carrara
Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)-guided ablation procedures are emerging as a minimally invasive therapeutic alternative to radiological and surgical treatments for locally advanced pancreatic cancer (LAPC), pancreatic neuroendocrine tumours (PNETs), and pancreatic cystic lesions (PCLs). The advantages of treatment under endoscopic control are the real-time imaging guidance and the possibility to reach a deep target like the pancreas. Currently, radiofrequency probes specifically designed for ERCP or EUS ablation are available as well as hybrid cryotherm probe combining radiofrequency with cryotechnology...
February 16, 2017: World Journal of Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28250131/measles-virus-enters-breast-and-colon-cancer-cell-lines-through-a-pvrl4-mediated-macropinocytosis-pathway
#17
Sebastien Delpeut, Gary Sisson, Karen M Black, Christopher D Richardson
Measles virus (MeV) is a member of the family Paramixoviridae that causes a highly contagious respiratory disease, but has emerged as a promising oncolytic platform. Previous studies of MeV entry have focused on the identification of cellular receptors. However, the endocytic and trafficking pathways utilized during MeV entry remain poorly described. The contribution of each endocytic pathway has been examined in cells that express MeV receptors, SLAM (Signaling Lymphocyte-Activating Molecule) and PVRL4 (Poliovirus Receptor-Like-4, nectin-4)...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28250120/a-strategy-for-cultivation-of-retargeted-oncolytic-hsvs-in-non-cancer-cells
#18
Valerio Leoni, Valentina Gatta, Costanza Casiraghi, Alfredo Nicosia, Biljana Petrovic, Gabriella Campadelli-Fiume
The oncolytic herpes simplex virus (HSV) approved for clinical practice, and those in clinical trials are attenuated viruses, often deleted in the neurovirulence gene γ134.5, and in additional genes. A strategy to engineer non-attenuated oncolytic HSVs consists in retargeting the virus tropism to a cancer-specific receptor of choice - exemplified by HER2 (human epidermal growth factor receptor 2) present in breast, ovary and other cancers - and in detargeting from the natural receptors. Because the HER2-retargeted HSVs strictly depend on this receptor for infection, the viruses employed in preclinical studies were cultivated in HER2-positive cancer cells...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28248314/spatiotemporally-restricted-arenavirus-replication-induces-immune-surveillance-and-type-i-interferon-dependent-tumour-regression
#19
Halime Kalkavan, Piyush Sharma, Stefan Kasper, Iris Helfrich, Aleksandra A Pandyra, Asmae Gassa, Isabel Virchow, Lukas Flatz, Tim Brandenburg, Sukumar Namineni, Mathias Heikenwalder, Bastian Höchst, Percy A Knolle, Guido Wollmann, Dorothee von Laer, Ingo Drexler, Jessica Rathbun, Paula M Cannon, Stefanie Scheu, Jens Bauer, Jagat Chauhan, Dieter Häussinger, Gerald Willimsky, Max Löhning, Dirk Schadendorf, Sven Brandau, Martin Schuler, Philipp A Lang, Karl S Lang
Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models...
March 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28246027/recombinant-newcastle-disease-virus-expressing-human-trail-as-a-potential-candidate-for-hepatoma-therapy
#20
Yunzhou Wu, Jinjiao He, Jingshu Geng, Ying An, Xianlong Ye, Shijun Yan, Qingzhong Yu, Jiechao Yin, Zhenyu Zhang, Deshan Li
Newcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently proved for clinical trials. We have previously reported, for the first time, NDV Anhinga strain has an efficient cancer therapeutic efficacy in hepatoma. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent...
February 27, 2017: European Journal of Pharmacology
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