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Oncolytic virotherapy in glioblastoma

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https://read.qxmd.com/read/30775418/measles-virus-based-treatments-trigger-a-pro-inflammatory-cascade-and-a-distinctive-immunopeptidome-in-glioblastoma
#1
Srinath Rajaraman, Denis Canjuga, Michael Ghosh, Marius Cosmin Codrea, Raika Sieger, Florian Wedekink, Marcos Tatagiba, Marilin Koch, Ulrich M Lauer, Sven Nahnsen, Hans-Georg Rammensee, Michael D Mühlebach, Stefan Stevanovic, Ghazaleh Tabatabai
Glioblastoma is an aggressive primary brain tumor with bad prognosis. On the other hand, oncolytic measles virus (MeV) therapy is an experimental glioma treatment strategy with clinical safety and first evidence of anti-tumoral efficacy. Therefore, we investigated the combination of MeV with conventional therapies by cytotoxic survival assays in long-term glioma cell lines LN229, LNZ308, and glioma stem-like GS8 cells, as well as the basal viral infectivity in primary glioblastoma cultures T81/16, T1094/17, and T708/16...
March 29, 2019: Molecular Therapy Oncolytics
https://read.qxmd.com/read/30755732/eradication-of-glioblastoma-by-immuno-virotherapy-with-a-retargeted-oncolytic-hsv-in-a-preclinical-model
#2
Francesco Alessandrini, Laura Menotti, Elisa Avitabile, Irene Appolloni, Davide Ceresa, Daniela Marubbi, Gabriella Campadelli-Fiume, Paolo Malatesta
Oncolytic herpes simplex viruses are proving to be effective in clinical trials against a number of cancers. Here, R-115, an oncolytic herpes simplex virus retargeted to human erbB-2, fully virulent in its target cells, and armed with murine interleukin-12 was evaluated in a murine model of glioblastoma. We show that a single R-115 injection in established tumors resulted, in about 30% of animals, in the complete eradication of the tumor, otherwise invariably lethal. The treatment also induced a significant improvement in the overall median survival time of mice and a resistance to recurrence from the same neoplasia...
February 12, 2019: Oncogene
https://read.qxmd.com/read/30563098/recent-advances-in-oncolytic-virotherapy-and-immunotherapy-for-glioblastoma-a-glimmer-of-hope-in-the-search-for-an-effective-therapy
#3
REVIEW
Aleksei A Stepanenko, Vladimir P Chekhonin
To date, no targeted drugs, antibodies or combinations of chemotherapeutics have been demonstrated to be more efficient than temozolomide, or to increase efficacy of standard therapy (surgery, radiotherapy, temozolomide, steroid dexamethasone). According to recent phase III trials, standard therapy may ensure a median overall survival of up to 18⁻20 months for adult patients with newly diagnosed glioblastoma. These data explain a failure of positive non-controlled phase II trials to predict positive phase III trials and should result in revision of the landmark Stupp trial as a historical control for median overall survival in non-controlled trials...
December 5, 2018: Cancers
https://read.qxmd.com/read/30475349/an-oncolytic-herpesvirus-expressing-e-cadherin-improves-survival-in-mouse-models-of-glioblastoma
#4
Bo Xu, Rui Ma, Luke Russell, Ji Young Yoo, Jianfeng Han, Hanwei Cui, Ping Yi, Jianying Zhang, Hiroshi Nakashima, Hongsheng Dai, E Antonio Chiocca, Balveen Kaur, Michael A Caligiuri, Jianhua Yu
The efficacy of oncolytic herpes simplex virus (oHSV) is limited by rapid viral clearance by innate immune effector cells and poor intratumoral viral spread. We combine two approaches to overcome these barriers: inhibition of natural killer (NK) cells and enhancement of intratumoral viral spread. We engineered an oHSV to express CDH1, encoding E-cadherin, an adherent molecule and a ligand for KLRG1, an inhibitory receptor expressed on NK cells. In vitro, infection with this engineered virus, named OV-CDH1, induced high surface E-cadherin expression on infected glioblastoma (GBM) cells, which typically lack endogenous E-cadherin...
November 26, 2018: Nature Biotechnology
https://read.qxmd.com/read/30224769/enhanced-sensitivity-of-patient-derived-pediatric-high-grade-brain-tumor-xenografts-to-oncolytic-hsv-1-virotherapy-correlates-with-nectin-1-expression
#5
Gregory K Friedman, Joshua D Bernstock, Dongquan Chen, Li Nan, Blake P Moore, Virginia M Kelly, Samantha L Youngblood, Catherine P Langford, Xiaosi Han, Eric K Ring, Elizabeth A Beierle, G Yancey Gillespie, James M Markert
Pediatric high-grade brain tumors and adult glioblastoma are associated with significant morbidity and mortality. Oncolytic herpes simplex virus-1 (oHSV) is a promising approach to target brain tumors; oHSV G207 and M032 (encodes human interleukin-12) are currently in phase I clinical trials in children with malignant supratentorial brain tumors and adults with glioblastoma, respectively. We sought to compare the sensitivity of patient-derived pediatric malignant brain tumor and adult glioblastoma xenografts to these clinically-relevant oHSV...
September 17, 2018: Scientific Reports
https://read.qxmd.com/read/29796615/oncolytic-virotherapy-in-glioblastoma-patients-induces-a-tumor-macrophage-phenotypic-shift-leading-to-an-altered-glioblastoma-microenvironment
#6
Wouter B L van den Bossche, Anne Kleijn, Charlotte E Teunissen, Jane S A Voerman, Cristina Teodosio, David P Noske, Jacques J M van Dongen, Clemens M F Dirven, Martine L M Lamfers
Background: Immunosuppressive protumoral M2 macrophages are important in pathogenesis, progression, and therapy resistance in glioblastoma (GBM) and provide a target for therapy. Recently oncolytic virotherapy in murine models was shown to change these M2 macrophages toward the pro-inflammatory and antitumoral M1 phenotype. Here we study the effects of the oncolytic virotherapy Delta24-RGD in humans, using both in vitro models and patient material. Methods: Human monocyte-derived macrophages were co-cultured with Delta24-RGD-infected primary glioma stem-like cells (GSCs) and were analyzed for their immunophenotype, cytokine expression, and secretion profiles...
October 9, 2018: Neuro-oncology
https://read.qxmd.com/read/29788332/constitutive-interferon-pathway-activation-in-tumors-as-an-efficacy-determinant-following-oncolytic-virotherapy
#7
Cheyne Kurokawa, Ianko D Iankov, S Keith Anderson, Ileana Aderca, Alexey A Leontovich, Matthew J Maurer, Ann L Oberg, Mark A Schroeder, Caterina Giannini, Suzanne M Greiner, Marc A Becker, E Aubrey Thompson, Paul Haluska, Mark E Jentoft, Ian F Parney, S John Weroha, Jin Jen, Jann N Sarkaria, Evanthia Galanis
Background: Attenuated measles virus (MV) strains are promising agents currently being tested against solid tumors or hematologic malignancies in ongoing phase I and II clinical trials; factors determining oncolytic virotherapy success remain poorly understood, however. Methods: We performed RNA sequencing and gene set enrichment analysis to identify pathways differentially activated in MV-resistant (n = 3) and -permissive (n = 2) tumors derived from resected human glioblastoma (GBM) specimens and propagated as xenografts (PDX)...
October 1, 2018: Journal of the National Cancer Institute
https://read.qxmd.com/read/29599413/combinatorial-effects-of-vegfr-kinase-inhibitor-axitinib-and-oncolytic-virotherapy-in-mouse-and-human-glioblastoma-stem-like-cell-models
#8
Dipongkor Saha, Hiroaki Wakimoto, Cole W Peters, Slawomir J Antoszczyk, Samuel D Rabkin, Robert L Martuza
Purpose: Glioblastoma (GBM), a fatal brain cancer, contains a subpopulation of GBM stem-like cells (GSCs) that contribute to resistance to current therapy. Angiogenesis also plays a key role in GBM progression. Therefore, we developed a strategy to target the complex GBM microenvironment, including GSCs and tumor vasculature. Experimental Design: We evaluated the cytotoxic effects of VEFGR tyrosine kinase inhibitor (TKI) axitinib in vitro and then tested antitumor efficacy of axitinib in combination with oncolytic herpes simplex virus (oHSV) expressing antiangiogenic cytokine murine IL12 (G47Δ-mIL12) in two orthotopic GSC-derived GBM models: patient-derived recurrent MGG123 GSCs, forming vascular xenografts in immunodeficient mice; and mouse 005 GSCs, forming syngeneic tumors in immunocompetent mice...
July 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://read.qxmd.com/read/29536305/virotherapy-of-the-malignant-u87-human-glioblastoma-in-the-orthotopic-xenotransplantation-mouse-scid-model
#9
S N Shchelkunov, I A Razumov, I V Kolosova, A V Romashchenko, E L Zavjalov
The possibility of glioblastoma virotherapy at intravenous injection of the LIVP-GFP recombinant virus was studied in experimental model of orthotopic xenotransplantation of human glioblastoma cell line U87 to SCID laboratory mice. The LIVP-GFP recombinant virus deficient for thymidine kinase exhibited a significantly greater oncolytic capacity than the original LIVP virus, and an intravenous injection of LIVP-GFP at the early stages of tumorigenesis in mouse brain in most cases resulted in the lysis of the tumor...
January 2018: Doklady. Biochemistry and Biophysics
https://read.qxmd.com/read/29179527/hitting-the-nail-on-the-head-combining-oncolytic-adenovirus-mediated-virotherapy-and-immunomodulation-for-the-treatment-of-glioma
#10
REVIEW
Wojciech K Panek, J Robert Kane, Jacob S Young, Aida Rashidi, Julius W Kim, Deepak Kanojia, Maciej S Lesniak
Glioblastoma is a highly aggressive malignant brain tumor with a poor prognosis and the median survival 14.6 months. Immunomodulatory proteins and oncolytic viruses represent two treatment approaches that have recently been developed for patients with glioblastoma that could extend patient survival and result in better treatment outcomes for patients with this disease. Together, these approaches could potentially augment the treatment efficacy and strength of these anti-tumor therapies. In addition to oncolytic activities, this combinatory approach introduces immunomodulation locally only where cancerous cells are present...
October 24, 2017: Oncotarget
https://read.qxmd.com/read/29118089/oncolytic-virotherapy-blockade-by-microglia-and-macrophages-requires-stat1-3
#11
Zahid M Delwar, Yvonne Kuo, Yan H Wen, Paul S Rennie, William Jia
The first oncolytic virotherapy employing HSV-1 (oHSV-1) was approved recently by the FDA to treat cancer, but further improvements in efficacy are needed to eradicate challenging refractory tumors, such as glioblastomas (GBM). Microglia/macrophages comprising approximately 40% of a GBM tumor may limit virotherapeutic efficacy. Here, we show these cells suppress oHSV-1 growth in gliomas by internalizing the virus through phagocytosis. Internalized virus remained capable of expressing reporter genes while viral replication was blocked...
February 1, 2018: Cancer Research
https://read.qxmd.com/read/28967558/oncolytic-h-1-parvovirus-shows-safety-and-signs-of-immunogenic-activity-in-a-first-phase-i-iia-glioblastoma-trial
#12
Karsten Geletneky, Jacek Hajda, Assia L Angelova, Barbara Leuchs, David Capper, Andreas J Bartsch, Jan-Oliver Neumann, Tilman Schöning, Johannes Hüsing, Birgit Beelte, Irina Kiprianova, Mandy Roscher, Rauf Bhat, Andreas von Deimling, Wolfgang Brück, Alexandra Just, Veronika Frehtman, Stephanie Löbhard, Elena Terletskaia-Ladwig, Jeremy Fry, Karin Jochims, Volker Daniel, Ottheinz Krebs, Michael Dahm, Bernard Huber, Andreas Unterberg, Jean Rommelaere
Oncolytic virotherapy may be a means of improving the dismal prognosis of malignant brain tumors. The rat H-1 parvovirus (H-1PV) suppresses tumors in preclinical glioma models, through both direct oncolysis and stimulation of anticancer immune responses. This was the basis of ParvOryx01, the first phase I/IIa clinical trial of an oncolytic parvovirus in recurrent glioblastoma patients. H-1PV (escalating dose) was administered via intratumoral or intravenous injection. Tumors were resected 9 days after treatment, and virus was re-administered around the resection cavity...
December 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://read.qxmd.com/read/28931212/temozolomide-resistant-human-brain-tumor-stem-cells-are-susceptible-to-recombinant-vesicular-stomatitis-virus-and-double-deleted-vaccinia-virus-in-vitro
#13
Bin Jiang, Xueqing Lun, Xiaoguang Hao, Yihua Wang, Xin Yin, Dezhang Huang, Wei He, Zhigang Wang
BACKGROUND: Malignant glioma still has a poor prognosis and remains incurable. Although temozolomide (TMZ) has demonstrated antitumor activity, its use recently has been halted because of some patients' resistance to this drug. New treatments are desperately needed. An oncolytic virus (virotherapy) is being developed as a novel cancer therapy. We have previously reported that recombinant Vesicular Stomatitis Virus (VSV-ΔM51) and double deleted Vaccinia Virus (vvDD) infected and killed glioma cell lines in vitro and prolonged survival in animal glioma models...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/28874392/zika-virus-has-oncolytic-activity-against-glioblastoma-stem-cells
#14
Zhe Zhu, Matthew J Gorman, Lisa D McKenzie, Jiani N Chai, Christopher G Hubert, Briana C Prager, Estefania Fernandez, Justin M Richner, Rong Zhang, Chao Shan, Eric Tycksen, Xiuxing Wang, Pei-Yong Shi, Michael S Diamond, Jeremy N Rich, Milan G Chheda
Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells...
October 2, 2017: Journal of Experimental Medicine
https://read.qxmd.com/read/28810147/macrophage-polarization-contributes-to-glioblastoma-eradication-by-combination-immunovirotherapy-and-immune-checkpoint-blockade
#15
Dipongkor Saha, Robert L Martuza, Samuel D Rabkin
Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells while inducing anti-tumor immunity. oHSV G47Δ expressing murine IL-12 (G47Δ-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Δ-mIL12 cured most mice in two glioma models...
August 14, 2017: Cancer Cell
https://read.qxmd.com/read/28810141/a-viro-immunotherapy-triple-play-for-the-treatment-of-glioblastoma
#16
COMMENT
John C Bell, Carolina S Ilkow
In this issue of Cancer Cell, Saha et al. systematically test and optimize combination therapy strategies in a challenging model of glioblastoma. Durable complete responses were seen only when an oncolytic virus expressing IL12 was coupled with anti-CTLA-4 and anti-PD-1 therapeutics.
August 14, 2017: Cancer Cell
https://read.qxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#17
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
December 1, 2017: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/28567859/therapeutic-targeting-of-chemoresistant-and-recurrent-glioblastoma-stem-cells-with-a-proapoptotic-variant-of-oncolytic-herpes-simplex-virus
#18
Nusrat Jahan, Jae M Lee, Khalid Shah, Hiroaki Wakimoto
Temozolomide (TMZ) chemotherapy, in combination with maximal safe resection and radiotherapy, is the current standard of care for patients with glioblastoma (GBM). Despite this multimodal approach, GBM inevitably relapses primarily due to resistance to chemo-radiotherapy, and effective treatment is not available for recurrent disease. In this study we identified TMZ resistant patient-derived primary and previously treated recurrent GBM stem cells (GSC), and investigated the therapeutic activity of a pro-apoptotic variant of oHSV (oHSV-TRAIL) in vitro and in vivo...
October 15, 2017: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/28376211/rad51-degradation-role-in-oncolytic-virus-poly-adp-ribose-polymerase-inhibitor-combination-therapy-in-glioblastoma
#19
Jianfang Ning, Hiroaki Wakimoto, Cole Peters, Robert L Martuza, Samuel D Rabkin
Background: Clinical success of poly(ADP-ribose) polymerase inhibitors (PARP i ) has been limited to repair-deficient cancers and by resistance. Oncolytic herpes simplex viruses (oHSVs) selectively kill cancer cells, irrespective of mutation, and manipulate DNA damage responses (DDR). Here, we explore potential synthetic lethal-like interactions between oHSV and PARP i . Methods: The efficacy of combining PARP i , oHSV MG18L, and G47Δ in killing patient-derived glioblastoma stem cells (GSCs) was assessed using cell viability assays and Chou-Talalay synergy analysis...
March 1, 2017: Journal of the National Cancer Institute
https://read.qxmd.com/read/28315557/oncolytic-viruses-treatment-and-implications-for-patients-with-gliomas
#20
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
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