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Oncolytic virus and t cells

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27610392/effect-of-hsv-il12-loaded-tumor-cell-based-vaccination-in-a-mouse-model-of-high-grade-neuroblastoma
#13
David F Bauer, Larisa Pereboeva, G Yancey Gillespie, Gretchen A Cloud, Osama Elzafarany, Catherine Langford, James M Markert, Lawrence S Lamb
We designed multimodal tumor vaccine that consists of irradiated tumor cells infected with the oncolytic IL-12-expressing HSV-1 virus, M002. This vaccine was tested against the syngeneic neuroblastoma mouse model Neuro 2a injected into the right caudate nucleus of the immunocompetent A/J mice. Mice were vaccinated via intramuscular injection of multimodal vaccine or uninfected irradiated tumor cells at seven and 14 days after tumor establishment. While there was no survival difference between groups vaccinated with cell-based vaccine applied following tumor injection, a premunition prime/boost vaccination strategy produced a significant survival advantage in both groups and sustained immune response to an intracranial rechallenge of the same tumor...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27514721/immunotherapy-of-melanoma
#14
D Kee, G McArthur
Immunotherapy for advanced melanoma has progressed dramatically in the last five years with the approval of immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Inhibition of these targets can break cancer-immune tolerance and result in durable objective responses with significantly improved tolerability over cytokine-based immunotherapy. Ipilimumab is an inhibitor of CTLA-4 and the first-in-class immune checkpoint inhibitor to demonstrate an improvement in overall survival in melanoma...
August 2, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27486853/oncolytic-virus-therapy-a-new-era-of-cancer-treatment-at-dawn
#15
REVIEW
Hiroshi Fukuhara, Yasushi Ino, Tomoki Todo
Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe...
October 2016: Cancer Science
https://www.readbyqxmd.com/read/27460757/immunotherapy-for-the-treatment-of-urothelial-carcinoma
#16
REVIEW
Nicholas M Donin, Andrew T Lenis, Stuart Holden, Alexandra Drakaki, Allan Pantuck, Arie Belldegrun, Karim Chamie
PURPOSE: We review the biological mechanisms of action, clinical safety and efficacy of immunotherapies for urothelial carcinoma. We also describe current areas of research in immunotherapy, and highlight ongoing trials and promising and novel investigational agents. MATERIALS AND METHODS: Data were obtained by a search of PubMed®, ClinicalTrials.gov and Cochrane databases for English language articles published through February 2016. Applicable abstracts from recent Society of Urologic Oncology, European Association of Urology, American Urological Association and ASCO® meetings were used...
July 25, 2016: Journal of Urology
https://www.readbyqxmd.com/read/27448784/novel-approaches-in-cancer-immunotherapy-a-light-at-the-end-of-the-tunnel
#17
Monika Joshi, Sumanta K Pal, Joseph J Drabick
After decades of disappointments, the use of immunotherapy in cancer has finally come of age and resulted in a real paradigm shift in cancer treatment across many tumor types. With the advent of novel immunotherapies based on increasing understanding of the human immune system, cure has become a real possibility for many patients. The development of cancer vaccines, immune checkpoint inhibitors, chimeric antigen receptor T cell, oncolytic virus based immunotherapy to name a few have given hope to patients. One of the most exciting developments in the era of immunotherapy has been the discovery of checkpoint inhibitors causing blockade of two important immune pathways -- cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death receptor-1 (PD-1), resulting in empowerment of anti-tumor immunity...
June 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27442441/preclinical-evaluation-of-advince-an-oncolytic-adenovirus-adapted-for-treatment-of-liver-metastases-from-neuroendocrine-cancer
#18
Di Yu, Justyna Leja-Jarblad, Angelica Loskog, Per Hellman, Valeria Giandomenico, Kjell Oberg, Magnus Essand
Cancer immunotherapy is becoming a cornerstone in the clinical care of cancer patients due to the breakthrough trials with immune checkpoint blockade antibodies and chimeric antigen receptor T cells. The next breakthrough in cancer immunotherapy is likely to be oncolytic viruses engineered to selectively kill tumor cells and deceive the immune system to believe that the tumor is a foreign entity that needs to be eradicated. We have developed AdVince, an oncolytic adenovirus for treatment of liver metastases from neuroendocrine tumor (NET)...
July 21, 2016: Neuroendocrinology
https://www.readbyqxmd.com/read/27435398/the-efficacy-of-oncolytic-adenovirus-is-mediated-by-t-cell-responses-against-virus-and-tumor-in-syrian-hamster-model
#19
Shengdian Wang, Xiaozhu Li, Pengju Wang, Hang Li, Xuexiang Du, Mingyue Liu, Qibin Huang, Yaohe Wang
: Purpose:Oncolytic adenoviruses (Ad) represent an innovative approach to cancer therapy. Its efficacy depends on multiple actions including direct tumor lysis, stimulation of antiviral and antitumor immune responses. In this study, we investigated the roles of T cell responses in oncolytic adenoviral therapy. EXPERIMENTAL DESIGN: An immunocompetent and viral replication-permissive Syrian hamster tumor model was used. The therapeutic mechanisms of oncolytic Ad were investigated by T-cell deletion, immunohistochemistry staining, and CTL assay...
July 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27393975/a-new-protoparvovirus-in-human-fecal-samples-and-cutaneous-t-cell-lymphomas-mycosis-fungoides
#20
Tung G Phan, Brigitte Dreno, Antonio Charlys da Costa, Linlin Li, Patricia Orlandi, Xutao Deng, Beatrix Kapusinszky, Juliana Siqueira, Anne-Chantal Knol, Franck Halary, Jacques Dantal, Kathleen A Alexander, Patricia A Pesavento, Eric Delwart
We genetically characterized seven nearly complete genomes in the protoparvovirus genus from the feces of children with diarrhea. The viruses, provisionally named cutaviruses (CutaV), varied by 1-6% nucleotides and shared ~76% and ~82% amino acid identity with the NS1 and VP1 of human bufaviruses, their closest relatives. Using PCR, cutavirus DNA was found in 1.6% (4/245) and 1% (1/100) of diarrhea samples from Brazil and Botswana respectively. In silico analysis of pre-existing metagenomics datasets then revealed closely related parvovirus genomes in skin biopsies from patients with epidermotropic cutaneous T-cell lymphoma (CTCL or mycosis fungoides)...
September 2016: Virology
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