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Oncolytic viruses

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https://www.readbyqxmd.com/read/28224120/oncolytic-virotherapy-including-rigvir-and-standard-therapies-in-malignant-melanoma
#1
REVIEW
Hani M Babiker, Irbaz Bin Riaz, Muhammad Husnain, Mitesh J Borad
The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor), nivolumab (IgG4 PD-1 inhibitor), pembrolizumab (IgG4 PD-1 inhibitor) and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor) and trametinib (MEK inhibitor), as they yielded improved responses and survival in malignant melanoma patients...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28223815/antitumor-effects-of-oncolytic-herpes-simplex-virus-type-2-against-colorectal-cancer-in-vitro-and-in-vivo
#2
Lei Yin, Chunhong Zhao, Jixia Han, Zengjun Li, Yanan Zhen, Ruixue Xiao, Zhongfa Xu, Yanlai Sun
BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28215147/approaches-to-optimize-gene-therapy-for-the-treatment-of-hematologic-malignancies-overcoming-the-obstacles
#3
Yingzhe Jiang, Bing Xia, Yizhuo Zhang, Wen Xu
Gene transfer and oncolytic viruses provide new therapeutic approaches for the treatment of hematologic malignancies. However, it is still too early to introduce gene delivery or oncolytic viruses into standard clinical protocol. It is very important to discuss the obstacles that gene transfer and oncolytic virotherapy face for the further clinical application for treatment of hematologic malignancies, and updating the advances made to overcome them. The major concerns in this review include the approaches of the development of immuno-stimulatory gene transfer mediated-vaccination for leukemia therapy, RNAi-based therapy for leukemia and enhancement of sensitivity of target malignant cells to virotherapy and alteration of host immune response to favor oncolytic viruses...
February 15, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28203643/establishing-elements-of-a-synthetic-biology-platform-for-vaccinia-virus-production-biobrick%C3%A2-design-serum-free-virus-production-and-microcarrier-based-cultivation-of-cv-1-cells
#4
Shuchang Liu, Ludmila Ruban, Yaohe Wang, Yuhong Zhou, Darren N Nesbeth
Vaccinia virus (VACV) is an established vector for vaccination and is beginning to prove effective as an oncolytic agent. Industrial production of VACV stands to benefit in future from advances made by synthetic biology in genome engineering and standardisation. The CV-1 cell line can be used for VACV propagation and has been used extensively with the CRISPR/Cas9 system for making precise edits of the VACV genome. Here we take first steps toward establishing a scalable synthetic biology platform for VACV production with CV-1 cells featuring standardised biological tools and serum free cell cultivation...
February 2017: Heliyon
https://www.readbyqxmd.com/read/28197384/oncolytic-measles-virus-induces-tumor-necrosis-factor-related-apoptosis-inducing-ligand-trail-mediated-cytotoxicity-by-human-myeloid-and-plasmacytoid-dendritic-cells
#5
Carole Achard, Jean-Baptiste Guillerme, Daniela Bruni, Nicolas Boisgerault, Chantal Combredet, Frédéric Tangy, Nolwenn Jouvenet, Marc Grégoire, Jean-François Fonteneau
Attenuated measles virus (MV) is currently being evaluated in clinical trials as an oncolytic therapeutic agent. Originally used for its lytic activity against tumor cells, it is now admitted that the effectiveness of MV also lies in its ability to initiate antitumor immune responses through the activation of dendritic cells (DCs). In this study, we investigated the capacity of oncolytic MV to convert human blood myeloid CD1c(+) DCs and plasmacytoid DCs (pDCs) into cytotoxic effectors. We found that MV induces the expression of the cytotoxic protein TNF-related apoptosis-inducing ligand (TRAIL) on the surface of DCs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194010/intratumoral-modulation-of-the-inducible-co-stimulator-icos-by-recombinant-oncolytic-virus-promotes-systemic-anti-tumour-immunity
#6
Dmitriy Zamarin, Rikke B Holmgaard, Jacob Ricca, Tamar Plitt, Peter Palese, Padmanee Sharma, Taha Merghoub, Jedd D Wolchok, James P Allison
Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression of T-cell co-stimulatory receptors, with the inducible co-stimulator (ICOS) being most notable. To explore ICOS as a direct target in the tumour, we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL)...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28192521/acquired-resistance-to-oxaliplatin-is-not-directly-associated-with-increased-resistance-to-dna-damage-in-sk-n-asroxali4000-a-newly-established-oxaliplatin-resistant-sub-line-of-the-neuroblastoma-cell-line-sk-n-as
#7
Emily Saintas, Liam Abrahams, Gulshan T Ahmad, Anu-Oluwa M Ajakaiye, Abdulaziz S H A M AlHumaidi, Candice Ashmore-Harris, Iain Clark, Usha K Dura, Carine N Fixmer, Chinedu Ike-Morris, Mireia Mato Prado, Danielle Mccullough, Shishir Mishra, Katia M U Schöler, Husne Timur, Maxwell D C Williamson, Markella Alatsatianos, Basma Bahsoun, Edith Blackburn, Catherine E Hogwood, Pamela E Lithgow, Michelle Rowe, Lyto Yiangou, Florian Rothweiler, Jindrich Cinatl, Richard Zehner, Anthony J Baines, Michelle D Garrett, Campbell W Gourlay, Darren K Griffin, William J Gullick, Emma Hargreaves, Mark J Howard, Daniel R Lloyd, Jeremy S Rossman, C Mark Smales, Anastasios D Tsaousis, Tobias von der Haar, Mark N Wass, Martin Michaelis
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin...
2017: PloS One
https://www.readbyqxmd.com/read/28188458/tanapoxvirus-lacking-the-15l-gene-inhibits-melanoma-cell-growth-in-vitro-by-inducing-interferon-%C3%AE-1-release
#8
Tiantian Zhang, Karim Essani
Oncolytic viruses (OVs) have emerged as a promising approach for melanoma treatment by causing tumor lysis and inducing immuno-modulatory activities. Tanapoxvirus (TPV), which causes a mild self-limiting disease in humans and contains a large DNA genome, appears as a promising OV candidate. TPV recombinants were generated with the thymidine kinase/66R gene deletion (TPVΔ66R), the 15L gene deletion (TPVΔ15L), or with both the 15L and 66R gene ablation (TPVΔ15LΔ66R). Our previous studies have shown that treatment of TPVΔ15L resulted in significant tumor regression in xenotransplanted human melanoma in nude mice...
February 10, 2017: Virus Genes
https://www.readbyqxmd.com/read/28185165/oncolytic-viruses-emerging-options-for-the-treatment-of-breast-cancer
#9
REVIEW
Yogesh R Suryawanshi, Tiantian Zhang, Karim Essani
Breast cancer (BC) is the most common type of cancer among women and is the second most common cause of cancer-related deaths, following lung cancer. Severe toxicity associated with a long-term use of BC chemo- and radiotherapy makes it essential to look for newer therapeutics. Additionally, molecular heterogeneity at both intratumoral and intertumoral levels among BC subtypes is known to result in a differential response to standard therapeutics. Oncolytic viruses (OVs) have emerged as one of the most promising treatment options for BC...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28178658/prime-boost-immunization-by-both-dna-vaccine-and-oncolytic-adenovirus-expressing-gm-csf-and-shrna-of-tgf-%C3%AE-2-induces-anti-tumor-immune-activation
#10
So Young Kim, Dongxu Kang, Hye Jin Choi, Yeonsoo Joo, Joo-Hang Kim, Jae J Song
A successful DNA vaccine for the treatment of tumors should break established immune tolerance to tumor antigen. However, due to the relatively low immunogenicity of DNA vaccines, compared to other kinds of vaccines using live virus or protein, a recombinant viral vector was used to enhance humoral and cellular immunity. In the current study, we sought to develop a novel anti-cancer agent as a complex of DNA and oncolytic adenovirus for the treatment of malignant melanoma in the C57BL/6 mouse model. MART1, a human melanoma-specific tumor antigen, was used to induce an increased immune reaction, since a MART1-protective response is required to overcome immune tolerance to the melanoma antigen MelanA...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176649/oncolytic-herpes-simplex-virus-vectors-fully-retargeted-to-tumor-associated-antigens
#11
Hiroaki Uchida, Hirofumi Hamada, Kenji Nakano, Heechung Kwon, Hideaki Tahara, Justus B Cohen, Joseph C Glorioso
Oncolytic virotherapy is a novel therapeutic modality for malignant diseases that exploits selective viral replication in cancer cells. Herpes simplex virus (HSV) is a promising agent for oncolytic virotherapy due to its broad cell tropism and the identification of mutations that favor its replication in tumor over normal cells. However, these attenuating mutations also tend to limit the potency of current oncolytic HSV vectors that have entered clinical studies. As an alternative, vector retargeting to novel entry receptors has the potential to achieve tumor specificity at the stage of virus entry, eliminating the need for replication-attenuating mutations...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176648/oncolytic-viruses-the-best-is-yet-to-come
#12
Chantal G Lemay, Brian A Keller, Robert E Edge, Masato Abei, John C Bell
Oncolytic viruses are a promising anti-cancer platform, achieving significant pre-clinical and clinical milestones in recent years. A full arsenal of selective, safe, and effective viruses has been developed with some emerging pre-clinical research focusing on optimizing these therapies in the face of remaining challenges, both in the bloodstream and in the tumour microenvironment. Herein we discuss the recent progress in pre-clinical virotherapy research to address these challenges, with special focus on innovative strategies that seek to complement the current strengths of virotherapy, ensuring an optimal multi-faceted attack on cancer...
February 6, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28159747/nk-cell-recruitment-is-necessary-for-eradication-of-peritoneal-carcinomatosis-with-an-il12-expressing-maraba-virus-cellular-vaccine
#13
Almohanad A Alkayyal, Lee-Hwa Tai, Michael A Kennedy, Christiano Tanese de Souza, Jiqing Zhang, Charles Lefebvre, Shalini Sahi, Abhirami A Ananth, Ahmad Bakur Mahmoud, Andrew P Makrigiannis, Greg O Cron, Blair Macdonald, E Celia Marginean, David F Stojdl, John C Bell, Rebecca C Auer
Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells...
February 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28147331/aurora-a-kinase-inhibition-enhances-oncolytic-herpes-virotherapy-through-cytotoxic-synergy-and-innate-cellular-immune-modulation
#14
Mark A Currier, Les Sprague, Tilat A Rizvi, Brooke Nartker, Chun-Yu Chen, Pin-Yi Wang, Brian J Hutzen, Meghan R Franczek, Ami V Patel, Katherine E Chaney, Keri A Streby, Jeffrey A Ecsedy, Joe Conner, Nancy Ratner, Timothy P Cripe
Malignant peripheral nerve sheath tumor (MPNST) and neuroblastoma models respond to the investigational small molecule Aurora A kinase inhibitor, alisertib. We previously reported that MPNST and neuroblastomas are also susceptible to oncolytic herpes virus (oHSV) therapy. Herein, we show that combination of alisertib and HSV1716(HSV1716), a virus derived from HSV-1 and attenuated by deletion of RL1, exhibits significantly increased antitumor efficacy compared to either monotherapy. Alisertib and HSV1716 reduced tumor growth and increased survival in two xenograft models of MPNST and neuroblastoma...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143835/oncolytic-adenoviral-delivery-of-an-egfr-targeting-t-cell-engager-improves-antitumor-efficacy
#15
Carlos A Fajardo, Sonia Guedan, Luis A Rojas, Rafael Moreno, Marcel Arias-Badia, Jana de Sostoa, Carl H June, Ramon Alemany
Antiviral immune responses present a major hurdle to the efficacious use of oncolytic adenoviruses as cancer treatments. Despite the existence of a highly immunosuppressive tumor environment, adenovirus-infected cells can nonetheless be efficiently cleared by infiltrating cytotoxic T lymphocytes (CTL) without compromising tumor burden. In this study, we tested the hypothesis that tumor infiltrating T cells could be more effectively activated and redirected by oncolytic adenoviruses which were armed with bispecific T cell-engager antibodies (BiTE antibodies)...
January 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28138026/preclinical-evaluation-of-sequential-combination-of-oncolytic-adenovirus-delta-24-rgd-and-phosphatidylserine-targeting-antibody-in-pancreatic-ductal-adenocarcinoma
#16
Bingbing Dai, David Roife, Ya'an Kang, Joy Gumin, Mayrim V Rios Perez, Xinqun Li, Michael Pratt, Rolf A Brekken, Juan Fueyo-Margareto, Frederick F Lang, Jason B Fleming
Delta-24-RGD (DNX-2401) is a conditional replication-competent oncolytic virus engineered to preferentially replicate in and lyse tumor cells with abnormality of p16/RB/E2F pathway. In a phase 1 clinical trial, Delta-24-RGD has shown favorable safety profile and promising clinical efficacy in brain tumor, which prompted us to evaluate its anticancer activity in pancreatic ductal adenocarcinoma (PDAC), which also has high frequency of homozygous deletion and promoter methylation of CDKN2A encoding the p16 protein...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28135008/interferon-mediated-tumor-resistance-to-oncolytic-virotherapy
#17
Safieh Ebrahimi, Elnaz Ghorbani, Majid Khazaei, Amir Avan, Mikhail Ryzhikov, Keyhan Azadmanesh, Seyed Mahdi Hassanian
Interferons (INFs) elicit antiviral responses in tumor cells upon binding to cell surface receptors. Oncolytic virotherapy (OV) is an effective antitumor therapeutic approach which in combination with standard radiotherapy or chemotherapy regimens potentiates treatment responses in cancer patients. However, oncolytic viruses are susceptible to the IFN-induced antiviral state in the tumor microenvironment. A number of studies have therefore investigated the effects of combined therapy of IFN signaling pharmacological inhibitors with oncolytic viruses, which result in improved virus replication and oncolysis...
January 30, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28129716/potential-and-clinical-translation-of-oncolytic-measles-viruses
#18
Steven Robinson, Evanthia Galanis
Oncolytic viruses represent a novel treatment modality that is unencumbered by the standard resistance mechanisms limiting the therapeutic efficacy of conventional antineoplastic agents. Attenuated engineered measles virus strains derived from the Edmonston vaccine lineage have undergone extensive preclinical evaluation and have demonstrated an ability to infect, resulting in antitumor effect with a broad variety of malignancies. They have laid the foundation for multiple future clinical trials in both solid and hematologic malignancies, which have demonstrated safety, biologic activity and the ability to elicit antitumor immune responses...
January 27, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28114818/functional-screening-identifies-human-mirnas-that-modulate-adenovirus-propagation-in-prostate-cancer-cells
#19
Jasmina Hodzic, Daoud Sie, Annaleen Vermeulen, Victor W van Beusechem
Oncolytic adenoviruses represent a novel class of anticancer agents. Their efficacy in killing cancer cells is variable, suggesting that there is room for improvement. Host miRNAs have been shown to play important roles in susceptibility of cells to replication of different viruses. Here, we investigate if adenovirus replication in human prostate cancer cells is influenced by host cell miRNA expression. To this end, we analyzed human miRNA expression in response to adenovirus infection and performed functional screens for lytic adenovirus replication using synthetic miRNA mimic and inhibitor libraries...
January 23, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28114253/intratumoral-approaches-for-the-treatment-of-melanoma
#20
Praveen K Bommareddy, Ann W Silk, Howard L Kaufman
There have been significant advances in the immunotherapy of melanoma over the last decade. The tumor microenvironment is now known to promote an immune-suppressive milieu that can block effective immune-mediated tumor rejection. Several novel strategies designed to overcome local immunosuppression hold promise for treatment of melanoma and other cancers. These approaches include oncolytic viruses, plasmid DNA delivery, Toll-like receptor agonists, inflammatory dyes, cytokines, checkpoint inhibitors, immunomodulatory agents, and host and pathogenic cell-based vectors...
January 2017: Cancer Journal
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