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Oncolytic virus

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https://www.readbyqxmd.com/read/29350682/conditional-replication-of-oncolytic-viruses-based-on-detection-of-oncogenic-mrna
#1
REVIEW
M Renteln
Recently, split intein-based detection sensors for RNA have been developed that can target custom sequences in a modular fashion. If multi-region, multi-sample sequencing were to be applied to a patient's cancer, truncal (i.e., earliest-occurring) mutations could be identified and could serve as targets for these sense-and-respond modules. The next step would be to utilize an effective vector for treatment. A hyper-virulent herpes simplex virus could possibly serve as this vector, with concurrent immunosuppression to allow for unhindered infection of the tumor regions...
January 19, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29343567/parainfluenza-virus-infection-sensitizes-cancer-cells-to-dna-damaging-agents-implications-for-oncolytic-virus-therapy
#2
Candace R Fox, Griffith D Parks
We have previously shown that the Parainfluenza virus 5 (PIV5) mutant P/V-CPI- is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burden in mouse model systems. Here we show that P/V-CPI- infection of human laryngeal cancer HEp-2 cells results in the majority of the cells dying, but unexpectedly, over time there is an emergence of a population of cells which survive as P/V-CPI- persistently infected (PI) cells. P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability was highly dependent on activity of cellular inhibitors of apoptosis (IAPs) such as Survivin and XIAP...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29334764/development-of-gene-therapeutics-for-head-and-neck-cancer-in-china-from-bench-to-bedside
#3
Wei Guo, Hao Song
Head and neck cancer represents the seventh most common cancer worldwide. Multidisciplinary sequential treatment was performed in patients with head and neck cancer. However, there is an urgent need for a new treatment approach that can effectively improve the outcomes of head and neck cancer patients with advanced stage. Gene therapy is a rapidly evolving field with head and neck cancer. It has been proved a promising way to improve the efficacy of antitumor treatment. China is at the forefront in clinical trials and practice of gene therapies in the world...
January 15, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#4
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29327081/neutrophils-in-viral-infection
#5
REVIEW
Victor Naumenko, Madison Turk, Craig N Jenne, Seok-Joo Kim
Neutrophils are the first wave of recruited immune cells to sites of injury or infection and are crucial players in controlling bacterial and fungal infections. Although the role of neutrophils during bacterial or fungal infections is well understood, their impact on antiviral immunity is much less studied. Furthermore, neutrophil function in tumor pathogenesis and cancer treatment has recently received much attention, particularly within the context of oncolytic virus infection where neutrophils produce antitumor cytokines and enhance oncolysis...
January 11, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29326986/measles-virus-background-and-oncolytic-virotherapy
#6
REVIEW
Sankhajit Bhattacharjee, Pramod Kumar Yadava
Measles is a highly transmissible disease caused by measles virus and remains a major cause of child mortality in developing countries. Measles virus nucleoprotein (N) encapsidates the RNA genome of the virus for providing protection from host cell endonucleases and for specific recognition of viral RNA as template for transcription and replication. This protein is over-expressed at the time of viral replication. The C-terminal of N protein is intrinsically disordered, which enables this protein to interact with several host cell proteins...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29311387/critical-interactions-between-immunogenic-cancer-cell-death-oncolytic-viruses-and-the-immune-system-define-the-rational-design-of-combination-immunotherapies
#7
REVIEW
Jacob P van Vloten, Samuel T Workenhe, Sarah K Wootton, Karen L Mossman, Byram W Bridle
Oncolytic viruses (OVs) are multimodal cancer therapeutics, with one of their dominant mechanisms being in situ vaccination. There is a growing consensus that optimal cancer therapies should generate robust tumor-specific immune responses. Immunogenic cell death (ICD) is a paradigm of cellular demise culminating in the spatiotemporal release of danger-associated molecular patterns that induce potent anticancer immunity. Alongside traditional ICD inducers like anthracycline chemotherapeutics and radiation, OVs have emerged as novel members of this class of therapeutics...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29306950/immune-consequences-of-in-vitro-infection-of-human-peripheral-blood-leukocytes-with-vesicular-stomatitis-virus
#8
Tomasz Tomczyk, Grażyna Wróbel, Radosław Chaber, Iwona Siemieniec, Egbert Piasecki, Małgorzata Krzystek-Korpacka, Beata U Orzechowska
BACKGROUND: Oncolytic vesicular stomatitis virus (VSV) can be delivered intravenously to target primary and metastatic lesions, but the interaction between human peripheral blood leukocytes (PBLs) and VSV remains poorly understood. Our study aimed to assess the overall immunological consequences of ex vivo infection of PBLs with VSV. METHODS: Phenotypic analysis of lymphocyte subsets and apoptosis were evaluated with flow cytometry. Caspase 3/7 activity was detected by luminescence assay...
January 6, 2018: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29305707/transcriptional-retargeting-of-herpes-simplex-virus-for-cell-specific-replication-to-control-cancer
#9
REVIEW
Weihua Lou, Fang Ji, Jianing Fu, Zhiqiang Han, Wen Di, Ning Zhang
INTRODUCTION: Oncolytic virotherapy has emerged as a novel frontier in the treatment of cancer. Among the viruses that entered clinical trials are the oncolytic herpes simplex virus-1 (HSV-1). Current oncolytic HSV-1 approved for clinical practice, and those in clinical trials are attenuated viruses, often deleted in the neurovirulence gene γ134.5, and in additional genes, which may result in a much more attenuated virus with reduced replication efficiency. Therefore, the transcriptional retargeting strategy by modifying the regulator elements flanking essential viral genes to achieve tumor-specific replication while maintaining as much of the viral genome has been representing alternative promising oncolytic virotherapy modality...
January 5, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29304405/targeting-polysialic-acid-abundant-cancers-using-oncolytic-adenoviruses-with-fibers-fused-to-active-bacteriophage-borne-endosialidase
#10
Nikolas T Martin, Christoph Wrede, Julia Niemann, Jennifer Brooks, David Schwarzer, Florian Kühnel, Rita Gerardy-Schahn
Genetic replacement of adenoviral fiber knobs by ligands that enable tumor specific targeting of oncolytic adenoviruses is challenging because the fiber knob contributes to virus assembly. Here, we present a novel concept by describing stable recombinant adenoviruses with tumor specific infection mode. The fiber knob was replaced by endosialidaseNF (endoNF), the tailspike protein of bacteriophage K1F. EndoNF recognizes polysialic acid, an oncofetal antigen characteristic for high malignant tumors of neuroendocrine origin...
December 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/29298869/intravenous-delivery-of-oncolytic-reovirus-to-brain-tumor-patients-immunologically-primes-for-subsequent-checkpoint-blockade
#11
Adel Samson, Karen J Scott, David Taggart, Emma J West, Erica Wilson, Gerard J Nuovo, Simon Thomson, Robert Corns, Ryan K Mathew, Martin J Fuller, Timothy J Kottke, Jill M Thompson, Elizabeth J Ilett, Julia V Cockle, Philip van Hille, Gnanamurthy Sivakumar, Euan S Polson, Samantha J Turnbull, Elizabeth S Appleton, Gemma Migneco, Ailsa S Rose, Matthew C Coffey, Deborah A Beirne, Fiona J Collinson, Christy Ralph, D Alan Anthoney, Christopher J Twelves, Andrew J Furness, Sergio A Quezada, Heiko Wurdak, Fiona Errington-Mais, Hardev Pandha, Kevin J Harrington, Peter J Selby, Richard G Vile, Stephen D Griffin, Lucy F Stead, Susan C Short, Alan A Melcher
Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor response and patient survival are determined by tumor programmed death ligand 1 (PD-L1) expression. We hypothesized that preconditioning of the tumor immune microenvironment using targeted, virus-mediated interferon (IFN) stimulation would up-regulate tumor PD-L1 protein expression and increase cytotoxic T cell infiltration, improving the efficacy of subsequent checkpoint blockade...
January 3, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29298865/neoadjuvant-oncolytic-virotherapy-before-surgery-sensitizes-triple-negative-breast-cancer-to-immune-checkpoint-therapy
#12
Marie-Claude Bourgeois-Daigneault, Dominic Guy Roy, Amelia Sadie Aitken, Nader El Sayes, Nikolas Tim Martin, Oliver Varette, Theresa Falls, Lauren Elizabeth St-Germain, Adrian Pelin, Brian Dennis Lichty, David Francis Stojdl, Guy Ungerechts, Jean-Simon Diallo, John Cameron Bell
Triple-negative breast cancer (TNBC) is an aggressive disease for which treatment options are limited and associated with severe toxicities. Immunotherapeutic approaches like immune checkpoint inhibitors (ICIs) are a potential strategy, but clinical trials have demonstrated limited success in this patient cohort. Clinical studies using ICIs have revealed that patients with preexisting anticancer immunity are the most responsive. Given that oncolytic viruses (OVs) induce antitumor immunity, we investigated their use as an ICI-sensitizing approach...
January 3, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29298413/a-recombinant-antibody-expressing-influenza-virus-delays-tumor-growth-in-a-mouse-model
#13
Jennifer R Hamilton, Gayathri Vijayakumar, Peter Palese
Influenza A virus (IAV) has shown promise as an oncolytic agent. To improve IAV as an oncolytic virus, we sought to design a transgenic virus expressing an immune checkpoint-inhibiting antibody during the viral life cycle. To test whether it was possible to express an antibody during infection, an influenza virus was constructed encoding the heavy chain of an antibody on the PB1 segment and the light chain of an antibody on the PA segment. This antibody-expressing IAV grows to high titers, and the antibodies secreted from infected cells exhibit comparable functionality with hybridoma-produced antibodies...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29288575/high-titer-oncolytic-measles-production-process-by-integration-of-dielectric-spectroscopy-as-online-monitoring-system
#14
Tanja A Grein, Daniel Loewe, Hauke Dieken, Denise Salzig, Tobias Weidner, Peter Czermak
Oncolytic viruses offer new hope to millions of patients with incurable cancer. One promising class of oncolytic viruses is Measles virus, but its broad administration to cancer patients is currently hampered by the inability to produce the large amounts of virus needed for treatment (1010 -1012 virus particles per dose). Measles virus is unstable, leading to very low virus titers during production. The time of infection and time of harvest are therefore critical parameters in a Measles virus production process, and their optimization requires an accurate online monitoring system...
December 30, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29288515/a-third-generation-oncolytic-herpes-simplex-virus-inhibits-the-growth-of-liver-tumors-in-mice
#15
Richi Nakatake, Masaki Kaibori, Yusuke Nakamura, Yoshito Tanaka, Hideyuki Matushima, Tadayoshi Okumura, Takashi Murakami, Yasushi Ino, Tomoki Todo, Masanori Kon
Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. Oncolytic virus therapy is probably the next major breakthrough in cancer treatment. The third-generation oncolytic herpes simplex virus type 1 (HSV-1) T-01 kills tumor cells without damaging the surrounding normal tissues. Here we investigated the antitumor effects of T-01 on HCC and the host's immune response to HCC cells. The cytopathic activities of T-01 were tested in 14 human and one murine hepatoma cell lines in vitro...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29285820/maldi-imaging-detects-endogenous-digoxin-in-glioblastoma-cells-infected-by-zika-virus-would-it-be-the-oncolytic-key
#16
Estela de O Lima, Tatiane M Guerreiro, Carlos Fernando O R Melo, Diogo N de Oliveira, Daisy Machado, Marcelo Lancelloti, Rodrigo R Catharino
Recently, microcephaly cases have increased in Americas and have been matter of concern due to Zika virus (ZIKV) recent outbreak. Previous studies have shown that ZIKV-infected progenitor neuronal cells present morphological abnormalities and increased rates of cell death, which may be indicators of microcephaly causes. As recent studies indicate Zika virus' tropism for brain cells, how would a glioblastoma (GBM) lineage behave under ZIKV infection, considering GBM the most common and malignant brain tumor in adults, presenting extreme chemoresistance and high morbidity and mortality rates? The current trend of using genetically engineered oncolytic pathogens as a safe way to eliminate tumors is under development, with trials already in course...
December 28, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29284308/fighting-cancer-with-viruses-oncolytic-virus-therapy-in-china
#17
Ding Wei, Jing Xu, Xinyuan Liu, Zhi-Nan Chen, Huijie Bian
Oncolytic virus has the special property with selective infection of tumor cells, leading to oncolysis of cancer cells and minimal toxicity to normal tissues, which is administrated in cancer therapy called oncolytic virotherapy. As a biological agent, oncolytic virus could induce tumor cell lysis, local immunological reaction, and enhance systemic anti-tumor immunity. These immune stimulatory properties of oncolytic virus will provide enormous benefits to override cancer. Nowadays, a great variety of oncolytic viruses including genetically engineered and natural viruses have shown promise in preclinical models and clinical studies...
December 28, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29277767/antitumor-memory-t-cells-become-functionally-mature-from-30-to-100-days-in-a-mouse-model-of-neoplasia
#18
Yanhua Gao, Mamdouha A Barmada, Ira Bergman
BACKGROUND: Late metastases develop from cancer of the breast, prostate, lung, kidney and malignant melanomas. Memory T-cells have excellent potential to prevent this devastating development in the same way that they routinely prevent emergence of latent viruses. MATERIAL AND METHODS: A peritoneal tumor mouse model of viral oncotherapy was used to generate therapeutic antitumor memory T-cells. Functional in vivo and in vitro assays were used to study the temporal evolution of their anticancer effects...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29275471/oncolytic-virotherapy-and-the-tumor-microenvironment
#19
Sara E Berkey, Steve H Thorne, David L Bartlett
Oncolytic viral therapy is a promising approach to treat many malignancies, including breast, colorectal, hepatocellular, and melanoma. The best results are seen when using "targeted and armed" viruses. These are viruses that have been genetically modified to selectively replicate within cancer cells and express specific transgenes that alter the tumor microenvironment to inhibit tumor progression. The products of these transgenes induce cell death, make the virus less virulent, compromise tumor vascularity, and are capable of modulating or enhancing the immune system-such as cytokines and chemokines...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29275092/antitumor-benefits-of-antiviral-immunity-an-underappreciated-aspect-of-oncolytic-virotherapies
#20
REVIEW
Shashi Gujar, Jonathan G Pol, Youra Kim, Patrick W Lee, Guido Kroemer
Oncolytic viruses (OVs) represent a new class of cancer immunotherapeutics. Administration of OVs to cancer-bearing hosts induces two distinct immunities: antiviral and antitumor. While antitumor immunity is beneficial, antiviral immune responses are often considered detrimental for the efficacy of OV-based therapy. The existing dogma postulates that anti-OV immune responses restrict viral replication and spread, and thus reduce direct OV-mediated killing of cancer cells. Accordingly, a myriad of therapeutic strategies aimed at mitigating anti-OV immune responses is presently being tested...
December 20, 2017: Trends in Immunology
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