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Oncolytic virus and t cells

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https://www.readbyqxmd.com/read/28074746/oncology-s-trojan-horse-using-viruses-to-battle-cancer
#1
Heena J Mavani, Jeannette Y Wick
: In 2016, the American health care system was faced with more than 1.6 million new cases of cancer, and individuals older than 65 years of age will be affected disproportionately. Many older individuals are poor candidates for traditional treatments (e.g., chemotherapy, radiation) because of actual or potential treatment-related adverse events. Researchers continuously look for novel therapeutic strategies, and an exciting new one is on the horizon: virotherapy. Viruses' ability to infect and kill human cells makes them promising cancer treatments...
December 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28061981/talimogene-laherparepvec-t-vec-for-the-treatment-of-melanoma-and-other-cancers
#2
REVIEW
Claud Grigg, Zoë Blake, Robyn Gartrell, Adrian Sacher, Bret Taback, Yvonne Saenger
Talimogene laherparepvec (T-Vec) is the first live virus to be approved by the US Food and Drug Administration for the treatment of cancer. This engineered version of herpes simplex virus type 1 (HSV-1) is the product of decades of preclinical work aimed at identifying and modifying aspects of the viral genome involved in virulence and immunogenicity. T-Vec preferentially infects and lyses tumor cells and, in some cases, induces a systemic immune response against the tumor. These properties have translated into significant and durable clinical responses, particularly in advanced melanoma...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28054473/-screening-different-host-cell-lines-for-the-dynamic-production-of-measles-virus
#3
Tanja A Grein, Felix Schwebel, Marco Kress, Daniel Loewe, Hauke Dieken, Denise Salzig, Tobias Weidner, Peter Czermak
Measles virus (MV) has a natural affinity for cancer cells and oncolytic MV preparations have therefore been investigated in several clinical trials as a potential treatment for cancer. The main bottleneck in the administration of oncolytic MV to cancer patients is the production process, because very large doses of virus particles are required for each treatment. Here we investigated the productivity of different host cells and found that a high infection efficiency did not necessarily result in high virus yields because virus release is also dependent on the host cell...
January 5, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/27993141/colonization-of-xenograft-tumors-by-oncolytic-vaccinia-virus-vacv-results-in-enhanced-tumor-killing-due-to-the-involvement-of-myeloid-cells
#4
Mehmet Okyay Kilinc, Klaas Ehrig, Maysam Pessian, Boris R Minev, Aladar A Szalay
BACKGROUND: The mechanisms by which vaccinia virus (VACV) interacts with the innate immune components are complex and involve different mechanisms. iNOS-mediated NO production by myeloid cells is one of the central antiviral mechanisms and this study aims to investigate specifically whether iNOS-mediated NO production by myeloid cells, is involved in tumor eradication following the virus treatment. METHODS: Human colon adenocarcinoma (HCT-116) xenograft tumors were infected by VACV...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27989216/the-safety-of-talimogene-laherparepvec-for-the-treatment-of-advanced-melanoma
#5
Alexandra Gangi, Jonathan S Zager
Talimogene laherparepvec (T-VEC, IMLYGIC) is an oncolytic herpes virus type I used as intralesional therapy for the treatment of unresectable metastatic melanoma in a cutaneous, subcutaneous, or nodal location. Talimogene laherparepvec selectively replicates within and lyses tumor cells while producing granulocyte macrophage colony-stimulating factor (GM-CSF), which may promote an immune mediated antitumor response. Areas covered: The US Food and Drug Administration approved Talimogene laherparepvec in late 2015 following the completion of phase I, II and III trials that demonstrated safety and efficacy...
December 28, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27988837/talimogene-laherparepvec-t-vec-and-other-oncolytic-viruses-for-the-treatment-of-melanoma
#6
Praveen K Bommareddy, Anand Patel, Saamia Hossain, Howard L Kaufman
Many mammalian viruses have properties that can be commandeered for the treatment of cancer. These characteristics include preferential infection and replication in tumor cells, the initiation of tumor cell lysis, and the induction of innate and adaptive anti-tumor immunity. Furthermore, viruses can be genetically engineered to reduce pathogenicity and increase immunogenicity resulting in minimally toxic therapeutic agents. Talimogene laherparepvec (T-VEC; Imlygic™), is a genetically modified herpes simplex virus, type 1, and is the first oncolytic virus therapy to be approved for the treatment of advanced melanoma by the US FDA...
December 17, 2016: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/27966453/oncolytic-virus-synergizes-with-smac-mimetic-compounds-to-induce-rhabdomyosarcoma-cell-death-in-a-syngeneic-murine-model
#7
Christine C Dobson, Thet Naing, Shawn T Beug, Mame D Faye, Janelle Chabot, Martin St-Jean, Danielle E Walker, Eric C LaCasse, David F Stojdl, Robert G Korneluk, Martin Holcik
Rhabdomyosarcoma (RMS), a neoplasm characterized by undifferentiated myoblasts, is the most common soft tissue tumour in children. Therapeutic resistance is common in RMS and is often caused by acquired defects in the cellular apoptotic program. Smac mimetic compounds (SMCs) are a novel class of inhibitor of apoptosis (IAP) antagonists that are currently under clinical development as cancer therapeutics. We previously reported that cIAP1 is overexpressed in human primary RMS tumours and in patient-derived RMS cell lines where it drives resistance to apoptosis...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27933316/systemic-therapy-with-oncolytic-myxoma-virus-cures-established-residual-multiple-myeloma-in-mice
#8
Eric Bartee, Mee Y Bartee, Bjarne Bogen, Xue-Zhong Yu
Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. It has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells during autologous transplant...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#9
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27901098/tumor-specific-delivery-of-biologics-by-a-novel-t-cell-line-hozot
#10
Teppei Onishi, Hiroshi Tazawa, Yuuri Hashimoto, Makoto Takeuchi, Takeshi Otani, Shuji Nakamura, Fuminori Sakurai, Hiroyuki Mizuguchi, Hiroyuki Kishimoto, Yuzo Umeda, Yasuhiro Shirakawa, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
"Cell-in-cell" denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27875627/immunotherapy-approaches-in-the-treatment-of-malignant-brain-tumors
#11
REVIEW
Anastasie M Dunn-Pirio, Gordana Vlahovic
Glioblastoma is the most common malignant primary brain tumor. Despite standard-of-care treatment, consisting of maximal surgical resection followed by chemoradiation, both morbidity and mortality associated with this disease remain very poor. Therefore, there is an urgent need for more efficacious and well tolerated therapies. Advancing knowledge of the intricate interplay between malignant gliomas and the immune system, coupled with the recent launch of immunotherapy research for other cancers, has led to a veritable increase in immunotherapy investigation for glioblastoma and other malignant gliomas...
November 22, 2016: Cancer
https://www.readbyqxmd.com/read/27827454/novel-high-throughput-approach-for-purification-of-infectious-virions
#12
Kevin T James, Brad Cooney, Kate Agopsowicz, Mary Ann Trevors, Adil Mohamed, Don Stoltz, Mary Hitt, Maya Shmulevitz
Viruses are extensively studied as pathogens and exploited as molecular tools and therapeutic agents. Existing methods to purify viruses such as gradient ultracentrifugation or chromatography have limitations, for example demand for technical expertise or specialized equipment, high time consumption, and restricted capacity. Our laboratory explores mutations in oncolytic reovirus that could improve oncolytic activity, and makes routine use of numerous virus variants, genome reassortants, and reverse engineered mutants...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27784340/il-12-expressing-oncolytic-herpes-simplex-virus-promotes-anti-tumor-activity-and-immunologic-control-of-metastatic-ovarian-cancer-in-mice
#13
Eric D Thomas, Selene Meza-Perez, Kerri S Bevis, Troy D Randall, G Yancey Gillespie, Catherine Langford, Ronald D Alvarez
BACKGROUND: Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer...
October 27, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27779616/prime-boost-using-separate-oncolytic-viruses-in-combination-with-checkpoint-blockade-improves-anti-tumour-therapy
#14
E Ilett, T Kottke, J Thompson, K Rajani, S Zaidi, L Evgin, M Coffey, C Ralph, R Diaz, H Pandha, K Harrington, P Selby, R Bram, A Melcher, R Vile
The anti-tumour effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms, which depend both on the type of virus and the route of delivery. Here, we show that intra-tumoral oncolysis by Reovirus induced the priming of a CD8+, Th1-type anti-tumour response. By contrast, systemically delivered Vesicular Stomatitis Virus expressing a cDNA library of melanoma antigens (VSV-ASMEL) promoted a potent anti-tumour CD4+ Th17 response. Therefore, we hypothesised that combining the Reovirus-induced CD8+ T cell response, with the VSV-ASMEL CD4+ Th17 helper response, would produce enhanced anti-tumour activity...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27776794/oncolytic-influenza-a-virus-expressing-interleukin-15-decreases-tumor-growth-in%C3%A2-vivo
#15
Karin Hock, Johannes Laengle, Irina Kuznetsova, Andrej Egorov, Balazs Hegedus, Balazs Dome, Thomas Wekerle, Monika Sachet, Michael Bergmann
BACKGROUND: Interleukin-15 has become a promising molecule in the context of eliciting an effective, antitumor immune response because it is able to stimulate cells of the innate and adaptive immune system. METHODS: We generated an interleukin-15-expressing oncolytic influenza A virus for the treatment of an established murine tumor model. RESULTS: Our oncolytic influenza A virus produced large amounts of interleukin-15 and induced proliferation and activation of human T cells in vitro...
October 21, 2016: Surgery
https://www.readbyqxmd.com/read/27769635/immunotherapy-in-melanoma-recent-advances-and-future-directions
#16
REVIEW
C Franklin, E Livingstone, A Roesch, B Schilling, D Schadendorf
Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma...
September 2, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27736965/identification-of-optimal-insertion-site-in-recombinant-newcastle-disease-virus-rndv-vector-expressing-foreign-gene-to-enhance-its-anti-tumor-effect
#17
Ziye Pan, Jinjiao He, Lubna M Rasoul, Yunye Liu, Ruixiang Che, Yun Ding, Xiaocheng Guo, Jiarui Yang, Dehua Zou, Hua Zhang, Deshan Li, Hongwei Cao
Recombinant Newcastle disease virus (rNDV) is tumor selective and intrinsically oncolytic, which has been developed as a vector to express exogenous genes to enhance its oncolytic efficacy. Our previous studies found that insertion sites of foreign gene in rNDV vector affected its expression and anti-tumor activities. However, the optimal insertion site for foreign genes remains unknown. In this study, we inserted the enhanced green fluorescence protein (EGFP) and IL2 genes into four different intergenic regions of the rNDV using reverse genetics technology...
2016: PloS One
https://www.readbyqxmd.com/read/27680683/recurrent-loss-of-sting-signaling-in-melanoma-correlates-with-susceptibility-to-viral-oncolysis
#18
Tianli Xia, Hiroyasu Konno, Glen N Barber
The innate immune regulator STING stimulates cytokine production in response to the presence of cytosolic DNA, which can arise following DNA damage. Extrinsic STING signaling is also needed for antigen-presenting cells (APC) to stimulate antitumor T cell immunity. Here we show that STING signaling is recurrently suppressed in melanoma cells, where this event may enable immune escape after DNA damage. Mechanistically STING signaling was suppressed most frequently by epigenetic silencing of either STING or the cyclic GMP-AMP synthase (cGAS), which generates STING-activating cyclic dinucleotides (CDNs) after binding cytosolic DNA species...
September 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27663389/immunovirotherapy-with-measles-virus-strains-in-combination-with-anti-pd-1-antibody-blockade-enhances-antitumor-activity-in-glioblastoma-treatment
#19
Jayson Hardcastle, Lisa Mills, Courtney S Malo, Fang Jin, Cheyne Kurokawa, Hirosha Geekiyanage, Mark Schroeder, Jann Sarkaria, Aaron J Johnson, Evanthia Galanis
BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor and has a dismal prognosis. Measles virus (MV) therapy of GBM is a promising strategy due to preclinical efficacy, excellent clinical safety, and its ability to evoke antitumor pro-inflammatory responses. We hypothesized that combining anti- programmed cell death protein 1 (anti-PD-1) blockade and MV therapy can overcome immunosuppression and enhance immune effector cell responses against GBM, thus improving therapeutic outcome...
September 23, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27626058/expression-of-dai-by-an-oncolytic-vaccinia-virus-boosts-the-immunogenicity-of-the-virus-and-enhances-antitumor-immunity
#20
Mari Hirvinen, Cristian Capasso, Kilian Guse, Mariangela Garofalo, Andrea Vitale, Marko Ahonen, Lukasz Kuryk, Markus Vähä-Koskela, Akseli Hemminki, Vittorio Fortino, Dario Greco, Vincenzo Cerullo
In oncolytic virotherapy, the ability of the virus to activate the immune system is a key attribute with regard to long-term antitumor effects. Vaccinia viruses bear one of the strongest oncolytic activities among all oncolytic viruses. However, its capacity for stimulation of antitumor immunity is not optimal, mainly due to its immunosuppressive nature. To overcome this problem, we developed an oncolytic VV that expresses intracellular pattern recognition receptor DNA-dependent activator of IFN-regulatory factors (DAI) to boost the innate immune system and to activate adaptive immune cells in the tumor...
2016: Molecular Therapy Oncolytics
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