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Oncolytic virus and t cells

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https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#1
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/29311387/critical-interactions-between-immunogenic-cancer-cell-death-oncolytic-viruses-and-the-immune-system-define-the-rational-design-of-combination-immunotherapies
#2
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/29304405/targeting-polysialic-acid-abundant-cancers-using-oncolytic-adenoviruses-with-fibers-fused-to-active-bacteriophage-borne-endosialidase
#3
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
#4
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/29288515/a-third-generation-oncolytic-herpes-simplex-virus-inhibits-the-growth-of-liver-tumors-in-mice
#5
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/29277767/antitumor-memory-t-cells-become-functionally-mature-from-30-to-100-days-in-a-mouse-model-of-neoplasia
#6
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/29259007/amplification-of-oncolytic-vaccinia-virus-widespread-tumor-cell-killing-by-sunitinib-through-multiple-mechanisms
#7
Minah Kim, Maximilian Nitschké, Barbara Sennino, Patrizia Murer, Brian J Schriver, Alexander M Bell, Aishwarya Subramanian, Corry E McDonald, Jiahu Wang, Howard Cha, Marie-Claude Bourgeois-Daigneault, David H Kirn, John C Bell, Naomi De Silva, Caroline J Breitbach, Donald M McDonald
Oncolytic viruses pose many questions in their use in cancer therapy. In this study, we assessed the potential of mpJX-594 (mouse-prototype JX-594), a replication-competent vaccinia virus administered by intravenous injection, to target the tumor vasculature, produce immune activation and tumor cell killing more widespread than the infection, and suppress invasion and metastasis. These actions were examined in RIP-Tag2 transgenic mice with pancreatic neuroendocrine tumors (PNET) that developed spontaneously and progress as in humans...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29244745/immunotherapeutic-potential-of-oncolytic-h-1-parvovirus-hints-of-glioblastoma-microenvironment-conversion-towards-immunogenicity
#8
Assia L Angelova, Milena Barf, Karsten Geletneky, Andreas Unterberg, Jean Rommelaere
Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients...
December 15, 2017: Viruses
https://www.readbyqxmd.com/read/29238906/thyroid-dysfunctions-secondary-to-cancer-immunotherapy
#9
REVIEW
P Chalan, G Di Dalmazi, F Pani, A De Remigis, A Corsello, P Caturegli
BACKGROUND: Immunotherapy is a firmly established pillar in the treatment of cancer, alongside the traditional approaches of surgery, radiotherapy, and chemotherapy. Like every treatment, also cancer immunotherapy causes a diverse spectrum of side effects, collectively referred to as immune-related adverse events. OBJECTIVE: This review will examine the main forms of immunotherapy, the proposed mechanism(s) of action, and the incidence of thyroid dysfunctions. METHODS: A comprehensive MEDLINE search was performed for articles published up to March 30, 2017...
December 13, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29228368/the-oncolytic-virus-mg1-targets-and-eliminates-latently-hiv-1-infected-cells-implications-for-an-hiv-cure
#10
Nischal Ranganath, Teslin S Sandstrom, Stephanie C Burke Schinkel, Sandra C Côté, Jonathan B Angel
Latently HIV-infected cells evade immune- and drug-mediated clearance. These cells harbour intracellular signalling defects including impairment of the antiviral, type I IFN (IFN-I) response. Such defects have also been observed in several cancers, and have been exploited for the development of therapeutic oncolytic viruses, including the recombinant Maraba virus (MG1). We therefore hypothesized that MG1 would infect and eliminate latently HIV-1-infected cells, while sparing healthy uninfected cells. Preferential infection and elimination by MG1 was first demonstrated in latently HIV-1-infected cell lines...
December 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#11
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#12
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29209782/advances-in-immunotherapeutic-research-for-glioma-therapy
#13
REVIEW
Jeremy Tetsuo Miyauchi, Stella E Tsirka
Gliomas are primary malignancies of the brain. Tumors are staged based on malignancy, nuclear atypia, and infiltration of the surrounding brain parenchyma. Tumors are often diagnosed once patients become symptomatic, at which time the lesion is sizable. Glioblastoma (grade IV glioma) is highly aggressive and difficult to treat. Most tumors are diagnosed de novo. The gold standard of therapy, implemented over a decade ago, consists of fractionated radiotherapy and temozolomide, but unfortunately, chemotherapeutic resistance arises...
December 5, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/29208938/oncolytic-virotherapy-as-an-immunotherapeutic-strategy-for-multiple-myeloma
#14
REVIEW
Daniel E Meyers, Satbir Thakur, Chandini M Thirukkumaran, Don G Morris
Multiple Myeloma (MM), a clonal malignancy of antibody-producing plasma cells, is the second most common hematologic malignancy and results in significant patient morbidity and mortality. The high degree of immune dysregulation in MM, including T cell imbalances and up-regulation of immunosuppressive checkpoint proteins and myeloid derived suppressor cells, allows this malignancy to escape from host immune control. Despite advances in the therapeutic landscape of MM over the last decade, including the introduction of immunomodulatory drugs, the prognosis for this disease is poor, with less than 50% of patients surviving 5 years...
December 5, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/29179583/oncolytic-viruses-for-tumor-precision-imaging-and-radiotherapy
#15
Zi Jun Wu, Feng R Tang, Zhao-Wu Ma, Xiao-Chun Peng, Ying Xiang, Yanling Zhang, Jingbo Kang, Jiafu Ji, Xiao Q Liu, Xian-Wang Wang, Hong-Wu Xin, Bo X Ren
Dr. Peng et al invented the recombinant adenovirus expressing p53 (rAd-p53, Gendicine) for clinical tumor virotherapy in China in 2003, which is the first clinically approved gene therapy and tumor virotherapy drug in the world. An oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor (Talimogene laherparepvec, T-VEC) was approved for melanoma treatment in the United States in 2015. Since then, oncolytic viruses have been attracting more and more attention in the field of oncology, and may become novel significant modalities of tumor precision imaging and radiotherapy after further improvement...
November 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29179527/hitting-the-nail-on-the-head-combining-oncolytic-adenovirus-mediated-virotherapy-and-immunomodulation-for-the-treatment-of-glioma
#16
REVIEW
Wojciech K Panek, J Robert Kane, Jacob S Young, Aida Rashidi, Julius W Kim, Deepak Kanojia, Maciej S Lesniak
Glioblastoma is a highly aggressive malignant brain tumor with a poor prognosis and the median survival 14.6 months. Immunomodulatory proteins and oncolytic viruses represent two treatment approaches that have recently been developed for patients with glioblastoma that could extend patient survival and result in better treatment outcomes for patients with this disease. Together, these approaches could potentially augment the treatment efficacy and strength of these anti-tumor therapies. In addition to oncolytic activities, this combinatory approach introduces immunomodulation locally only where cancerous cells are present...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158470/comparative-oncology-evaluation-of-intravenous-recombinant-oncolytic-vesicular-stomatitis-virus-therapy-in-spontaneous-canine-cancer
#17
Shruthi Naik, Gina D Galyon, Nathan J Jenks, Michael B Steele, Amber C Miller, Sara D Allstadt, Lukkana Suksanpaisan, Kah Whye Peng, Mark J Federspiel, Stephen J Russell, Amy K LeBlanc
Clinical translation of intravenous therapies to treat disseminated or metastatic cancer is imperative. Comparative oncology, the evaluation of novel cancer therapies in animals with spontaneous cancer, can be utilized to inform and accelerate clinical translation. Preclinical murine studies demonstrate that single shot systemic therapy with a VSV-IFNβ-NIS, a novel recombinant oncolytic Vesicular stomatitis virus (VSV), can induce curative remission in tumor bearing mice. Clinical translation of VSV-IFNβ-NIS therapy is dependent on comprehensive assessment of clinical toxicities, virus shedding, pharmacokinetics, and efficacy in clinically relevant models...
November 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29157300/prospects-for-combined-use-of-oncolytic-viruses-and-car-t-cells
#18
REVIEW
Adam Ajina, John Maher
With the approval of talimogene laherparepvec (T-VEC) for inoperable locally advanced or metastatic malignant melanoma in the USA and Europe, oncolytic virotherapy is now emerging as a viable therapeutic option for cancer patients. In parallel, following the favourable results of several clinical trials, adoptive cell transfer using chimeric antigen receptor (CAR)-redirected T-cells is anticipated to enter routine clinical practice for the management of chemotherapy-refractory B-cell malignancies. However, CAR T-cell therapy for patients with advanced solid tumours has proved far less successful...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29076241/oncolytic-reovirus-therapy-pilot-study-in-dogs-with-spontaneously-occurring-tumours
#19
C C Hwang, M Igase, M Sakurai, T Haraguchi, K Tani, K Itamoto, T Shimokawa, M Nakaichi, Y Nemoto, S Noguchi, M Coffey, M Okuda, T Mizuno
Oncolytic virotherapy is a novel treatment involving replication-competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 10(8) to 5.0 × 10(9) TCID50 given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles...
October 27, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29061083/immuno-oncology-the-translational-runway-for-gene-therapy
#20
Ludger Weß, Frank Schnieders
Cancer therapy once again is experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing single targets or pathways only. Even the combination of several neo-antigens in cancer vaccines is not sufficient for a successful, lasting tumor eradication. The focus therefore has shifted on the immune systems role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells...
October 23, 2017: Human Gene Therapy
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