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Oncolytic viruses

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https://www.readbyqxmd.com/read/28814886/a-practical-guide-to-the-handling-and-administration-of-talimogene-laherparepvec-in-europe
#1
REVIEW
Kevin J Harrington, Olivier Michielin, Josep Malvehy, Isabella Pezzani Grüter, Lorna Grove, Anna Lisa Frauchiger, Reinhard Dummer
Talimogene laherparepvec is a herpes simplex virus-1-based intralesional oncolytic immunotherapy and is the first oncolytic virus to be approved in Europe. It is indicated for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (stage IIIB, IIIC, and IVM1a) with no bone, brain, lung, or other visceral disease. Talimogene laherparepvec is a genetically modified viral therapy, and its handling needs special attention due to its deep freeze, cold-chain requirements, its potential for viral shedding, and its administration by direct intralesional injection...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28812060/reolysin-and-histone-deacetylase-inhibition-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#2
Alena C Jaime-Ramirez, Jun-Ge Yu, Enrico Caserta, Ji Young Yoo, Jianying Zhang, Tae Jin Lee, Craig Hofmeister, John H Lee, Bhavna Kumar, Quintin Pan, Pawan Kumar, Robert Baiocchi, Theodoros Teknos, Flavia Pichiorri, Balveen Kaur, Matthew Old
Oncolytic viruses (OVs) are emerging as powerful anti-cancer agents and are currently being tested for their safety and efficacy in patients. Reovirus (Reolysin), a naturally occurring non-pathogenic, double-stranded RNA virus, has natural oncolytic activity and is being tested in phase I-III clinical trials in a variety of tumor types. With its recent US Food and Drug Administration (FDA) orphan drug designation for several tumor types, Reolysin is a potential therapeutic agent for various cancers, including head and neck squamous cell carcinomas (HNSCCs), which have a 5-year survival of ∼55%...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28810147/macrophage-polarization-contributes-to-glioblastoma-eradication-by-combination-immunovirotherapy-and-immune-checkpoint-blockade
#3
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://www.readbyqxmd.com/read/28810141/a-viro-immunotherapy-triple-play-for-the-treatment-of-glioblastoma
#4
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://www.readbyqxmd.com/read/28803259/opportunities-and-challenges-in-the-immunological-therapy-of-pediatric-malignancy-a-concise-snapshot
#5
REVIEW
Francesco Ceppi, Maja Beck-Popovic, Jean-Pierre Bourquin, Raffaele Renella
Over the last 50 years, collaborative clinical trials have reduced the number of children dying from pediatric cancer significantly. Unfortunately, certain tumor types have remained resistant to conventional surgical, radiotherapy and chemotherapy combinations, and relapsing and/or refractory disease remains associated with dismal outcomes. Recently, renewed attention has been given to the role for immunotherapies in pediatric oncology. In fact, these combine several attractive features, including (but possibly not limited to) the specificity for cancer cells, potentially in vivo persistence and longevity, and potency against refractory disease...
August 12, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#6
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...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28797937/immunohistochemical-characterization-and-sensitivity-to-human-adenovirus-serotypes-3-5-and-11p-of-new-cell-lines-derived-from-human-diffuse-grade-ii-to-iv-gliomas
#7
Minna Niittykoski, Mikael von Und Zu Fraunberg, Miika Martikainen, Tuomas Rauramaa, Arto Immonen, Susanna Koponen, Ville Leinonen, Markus Vähä-Koskela, Qiwei Zhang, Florian Kühnel, Ya-Fang Mei, Seppo Ylä-Herttuala, Juha E Jääskeläinen, Ari Hinkkanen
BACKGROUND: Oncolytic adenoviruses show promise in targeting gliomas because they do not replicate in normal brain cells. However, clinical responses occur only in a subset of patients. One explanation could be the heterogenic expression level of virus receptors. Another contributing factor could be variable activity of tumor antiviral defenses in different glioma subtypes. METHODS: We established a collection of primary low-passage cell lines from different glioma subtypes (3 glioblastomas, 3 oligoastrocytomas, and 2 oligodendrogliomas) and assessed them for receptor expression and sensitivity to human adenovirus (HAd) serotypes 3, 5, and 11p...
August 3, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28796556/systemic-virotherapy-for-multiple-myeloma
#8
Stefania Oliva, Manuela Gambella, Mario Boccadoro, Sara Bringhen
The multiple myeloma (MM) treatment scenario has changed considerably over the past few years. Several novel targeted therapies are currently under consideration including oncolytic virotherapy. Areas covered: This review provides an analysis of the mechanisms of action of virotherapy, and summarizes the preclinical and clinical studies of systemic virotherapy developed for the treatment of MM. Different types of viruses have been identified, including: adenovirus, vaccinia virus, herpes simplex virus 1, myxoma virus, reovirus, measles virus, vesicular stomatitis virus and coxsackievirus A21...
August 10, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28796161/comparison-of-liver-detargeting-strategies-for-systemic-therapy-with-oncolytic-adenovirus-serotype-5
#9
Tien V Nguyen, Mary E Barry, Mallory A Turner, Catherine M Crosby, Miguel A Trujillo, John C Morris, Michael A Barry
Oncolytic viruses would ideally be of use for systemic therapy to treat disseminated cancer. To do this safely, this may require multiple layers of cancer specificity. The pharmacology and specificity of oncolytic adenoviruses can be modified by (1) physical retargeting, (2) physical detargeting, (3) chemical shielding, or (4) by modifying the ability of viral early gene products to selectively activate in cancer versus normal cells. We explored the utility of these approaches with oncolytic adenovirus serotype 5 (Ad5) in immunocompetent Syrian hamsters bearing subcutaneous HaK tumors...
August 10, 2017: Biomedicines
https://www.readbyqxmd.com/read/28793793/making-oncolytic-virotherapy-a-clinical-reality-the-european-contribution
#10
Margaret R Duffy, Kerry D Fisher, Leonard W Seymour
Oncolytic viruses are quickly moving toward the forefront of modern medicines. The reward for the decades of research invested into developing viral platforms that selectively replicate in and lyse tumour cells whilst sparking anti-cancer adaptive immunity, is presenting in the form of durable therapeutic responses. Whilst it has certainly been a concerted global effort, in this review for the 25th anniversary of the ESGCT we will describe the current status of the major classes of oncolytic viruses, and focus on the contributions made by European researchers...
August 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28791656/egfr-as-a-target-for-glioblastoma-treatment-an-unfulfilled-promise
#11
Manfred Westphal, Cecile L Maire, Katrin Lamszus
The receptor for epidermal growth factor (EGFR) is a prime target for cancer therapy across a broad variety of tumor types. As it is a tyrosine kinase, small molecule tyrosine kinase inhibitors (TKIs) targeting signal transduction, as well as monoclonal antibodies against the EGFR, have been investigated as anti-tumor agents. However, despite the long-known enigmatic EGFR gene amplification and protein overexpression in glioblastoma, the most aggressive intrinsic human brain tumor, the potential of EGFR as a target for this tumor type has been unfulfilled...
August 8, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28791251/combining-oncolytic-adenovirus-with-radiation-a-paradigm-for-the-future-of-radiosensitization
#12
REVIEW
Sean M O'Cathail, Tzveta D Pokrovska, Timothy S Maughan, Kerry D Fisher, Leonard W Seymour, Maria A Hawkins
Oncolytic viruses and radiotherapy represent two diverse areas of cancer therapy, utilizing quite different treatment modalities and with non-overlapping cytotoxicity profiles. It is, therefore, an intriguing possibility to consider that oncolytic ("cancer-killing") viruses may act as cancer-selective radiosensitizers, enhancing the therapeutic consequences of radiation treatment on tumors while exerting minimal effects on normal tissue. There is a solid mechanistic basis for this potential synergy, with many viruses having developed strategies to inhibit cellular DNA repair pathways in order to protect themselves, during genome replication, from unwanted interference by cell processes that are normally triggered by DNA damage...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28789701/a-novel-bladder-cancer-specific-oncolytic-adenovirus-by-cd46-and-its-effect-combined-with-cisplatin-against-cancer-cells-of-car-negative-expression
#13
Wenjuan Cao, Junqiang Tian, Chong Li, Yanjun Gao, Xingchen Liu, Jianzhong Lu, Yuhan Wang, Zhiping Wang, Robert S Svatek, Ronald Rodriguez
BACKGROUND: Conditionally replicative oncolytic adenoviruses (CRAds) display significant anti-tumor effects. However, the traditional adenovirus of serotype 5 (Ad5) entering cancer cells via coxsackie virus and adenovirus receptor (CAR) can't be utilized for bladder cancer with low expression of CAR, which limits the application of Ad5. METHODS: We utilized Ad5/F11p containing the chimeric fiber gene encoding the Ad5 fiber tail domain and Ad11p fiber shaft and knob domains to construct bladder cancer-specific chimeric type viruses Ad5/F11p-PSCAE-UPII-E1A, which can infect bladder cancer cells mediated by CD46 molecule...
August 8, 2017: Virology Journal
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#14
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28766058/bioselection-of-coxsackievirus-b6-strain-variants-with-altered-tropism-to-human-cancer-cell-lines
#15
Victor A Svyatchenko, Vladimir A Ternovoy, Nikolai N Kiselev, Anna V Demina, Valery B Loktev, Sergey V Netesov, Peter M Chumakov
Cancer cells develop increased sensitivity to members of many virus families and, in particular, can be efficiently infected and lysed by many low-pathogenic human enteroviruses. However, because of their great genetic heterogeneity, cancer cells display different levels of sensitivity to particular enterovirus strains, which may substantially limit the chances of a positive clinical response. We show that a non-pathogenic strain of coxsackievirus B6 (LEV15) can efficiently replicate to high titers in the malignant human cell lines C33A, DU145, AsPC-1 and SK-Mel28, although it displays much lower replication efficiency in A431 and A549 cells and very limited replication ability in RD and MCF7 cells, as well as in the normal lung fibroblast cell line MRC-5 and the immortalized mammary epithelial cell line MCF10A...
August 1, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28763890/-oncolytic-property-of-hsv-1-recombinant-viruses-carrying-the-human-il-12
#16
X J Liu, X Y Wang, J X Guo, H J Zhu, C R Zhang, Z H Ma
Objective: Constructed the recombinant HSV-1 deleted ICP47 and inserted human IL-12, and investigate the virus' replication ability and oncolytic property in vitro and vivo. Methods: The recombinant HSV-1 deleting ICP47 (MH1005) and then inserting human IL-12 (MH1006) were obtained with bacterial artificial chromosome technology.The replication ability and the efficiency of inhibiting tumor were detected in several nerve tumor cell lines infected with HSV-wt, MH1005 and MH1006 respectively.The murine tumor model was established by subcutaneous inoculation Neuro-2a cells on both sides of mice back respectively...
July 18, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28751892/sharpening-the-edge-for-precision-cancer-immunotherapy-targeting-tumor-antigens-through-oncolytic-vaccines
#17
REVIEW
Namit Holay, Youra Kim, Patrick Lee, Shashi Gujar
Cancer immunotherapy represents a promising, modern-age option for treatment of cancers. Among the many immunotherapies being developed, oncolytic viruses (OVs) are slowly moving to the forefront of potential clinical therapeutic agents, especially considering the fact that the first oncolytic virus was recently approved by the Food and Drug Administration for the treatment of melanoma. OVs were originally discovered for their ability to kill cancer cells, but they have emerged as unconventional cancer immunotherapeutics due to their ability to activate a long-term antitumor immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28750564/selective-antagonism-of-bcl-xl-potentiates-m1-oncolysis-by-enhancing-mitochondrial-apoptosis
#18
Yaqian Tan, Yuan Lin, Kai Li, Xiao Xiao, Jiankai Liang, Jing Cai, Li Guo, Chuntao Li, Wenbo Zhu, Fan Xing, Jialuo Mai, Jiayu Gu, Xiaohong Tan, Wei Yin, Bingzheng Lu, Pengxin Qiu, Xingwen Su, Mingshi Gao, Jun Hu, Songmin He, Ling Lu, Shoufang Gong, Guangmei Yan, Haipeng Zhang
Oncolytic virotherapy is a novel and intriguing treatment strategy for cancer therapy. However, the clinical potential of oncolytic virus as single agent is limited. M1 virus is a promising oncolytic virus that has been tested in preclinical studies. In this study, we investigated the effect of the combination use of M1 virus and Bcl-2 family inhibitors. A chemical compounds screening including ten Bcl-2 family inhibitors demonstrated that pan-Bcl-2 inhibitors selectively augmented M1 virus oncolysis in cancer cells at very low doses...
July 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28749907/immunotherapy-in-urothelial-cancer-part-1-t-cell-checkpoint-inhibition-in-advanced-or-metastatic-disease
#19
Steven S Yu, Tanya B Dorff, Leslie K Ballas, Sarmad Sadeghi, Eila C Skinner, David I Quinn
Cancer of the urothelium is the sixth most common cancer in the United States and is seen predominantly in men. Most cases of this disease present as non-muscle-invasive bladder cancer (NMIBC), with cancer recurrence or progression to muscle-invasive cancer in more than 50% of patients after initial therapy. NMIBC is an immune-responsive disease, as indicated by the use of intravesical bacillus Calmette-Guérin as treatment for more than 3 decades. More recently, immunotherapy has seen much progress in a variety of cancers, including advanced and metastatic bladder cancer, in which historical 5-year survival rates are approximately 15%...
June 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28725635/implications-of-micrornas-in-oncolytic-virotherapy
#20
REVIEW
Xavier Bofill-De Ros, Maria Rovira-Rigau, Cristina Fillat
MicroRNAs (miRNAs) are an abundant class of small non-coding RNA molecules (~22 nt) that can repress gene expression. Deregulation of certain miRNAs is widely recognized as a robust biomarker for many neoplasms, as well as an important player in tumorigenesis and the establishment of tumoral microenvironments. The downregulation of specific miRNAs in tumors has been exploited as a mechanism to provide selectivity to oncolytic viruses or gene-based therapies. miRNA response elements recognizing miRNAs expressed in specific tissues, but downregulated in tumors, have been inserted into the 3'UTR of viral genes to promote the degradation of these viral mRNAs in healthy tissue, but not in tumor cells...
2017: Frontiers in Oncology
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