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https://www.readbyqxmd.com/read/28428211/imaging-manifestations-of-pseudoprogression-in-metastatic-melanoma-nodes-injected-with-talimogene-laherparepvec-initial-experience
#1
C Zamora, M Lopez, F Cunningham, F Collichio, M Castillo
Talimogene laherparepvec is an oncolytic virus recently approved for targeted treatment of advanced melanoma. Because of an inflammatory reaction, treated lesions may increase in size and develop infiltrative margins that can be construed as disease progression or extracapsular spread. In this report, we describe our initial experience imaging the response of metastatic nodes injected with talimogene laherparepvec. Six of 12 nodes (50%) showed growth from baseline followed by decreased size, 5 of 12 nodes (42%) showed a downward size trend, and 1 node showed continued increase in size...
April 20, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28424330/combination-of-an-oncolytic-virus-with-pd-l1-blockade-keeps-cancer-in-check
#2
Brian A Jonas
An oncolytic vaccinia virus expressing CXCL11 combined with PD-L1 blockade significantly reduces tumor burden and improves survival in murine cancer models.
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28423057/insertion-of-a-ligand-to-her2-in-gb-retargets-hsv-tropism-and-obviates-the-need-for-activation-of-the-other-entry-glycoproteins
#3
Biljana Petrovic, Tatiana Gianni, Valentina Gatta, Gabriella Campadelli-Fiume
Herpes simplex virus (HSV) entry into the cells requires glycoproteins gD, gH/gL and gB, activated in a cascade fashion by conformational modifications induced by cognate receptors and intermolecular signaling. The receptors are nectin1 and HVEM (Herpes virus entry mediator) for gD, and αvβ6 or αvβ8 integrin for gH. In earlier work, insertion of a single chain antibody (scFv) to the cancer receptor HER2 (human epidermal growth factor receptor 2) in gD, or in gH, resulted in HSVs specifically retargeted to the HER2-positive cancer cells, hence in highly specific non-attenuated oncolytic agents...
April 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28417936/oncolytic-alphaviruses-in-cancer-immunotherapy
#4
REVIEW
Kenneth Lundstrom
Oncolytic viruses show specific targeting and killing of tumor cells and therefore provide attractive assets for cancer immunotherapy. In parallel to oncolytic viral vectors based on adenoviruses and herpes simplex viruses, oncolytic RNA viruses and particularly alphaviruses have been evaluated as delivery vehicles. Immunization studies in experimental rodent models for various cancers including glioblastoma, hematologic, hepatocellular, colon, cervix, and lung cancer as well as melanoma have been conducted with naturally occurring oncolytic alphavirus strains such as M1 and Sindbis AR339...
April 12, 2017: Vaccines
https://www.readbyqxmd.com/read/28409558/in-vitro-detection-of-cholangiocarcinoma-cells-using-a-fluorescent-protein-expressing-oncolytic-herpes-virus
#5
R J S Coelen, M J de Keijzer, R Weijer, V V Loukachov, J K Wiggers, F P J Mul, A C W A van Wijk, Y Fong, M Heger, T M van Gulik
Pathological confirmation is desired prior to high-risk surgery for suspected perihilar cholangiocarcinoma (PHC), but preoperative tissue diagnosis is limited by poor sensitivity of available techniques. This study aimed to validate whether a tumor-specific enhanced green fluorescent protein (eGFP)-expressing oncolytic virus could be used for cholangiocarcinoma (CC) cell detection. Extrahepatic CC cell lines SK-ChA-1, EGI-1, TFK-1 and control cells (primary human liver cells) were exposed to the oncolytic herpes simplex type 1 virus NV1066 for up to 24 h in adherent culture...
April 14, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28407327/oncolytic-viral-therapy-for-pancreatic-cancer
#6
REVIEW
Ahmad Rahal, Benjamin Musher
Outcomes of pancreatic adenocarcinoma (PDA) remain dismal despite extensive clinical investigation. Combination chemotherapy provides modest improvements in survival above best supportive care, and immunotherapy has thus far not proven effective. Nevertheless, growing insight into antitumor immunity and the tumor microenvironment has inspired the discovery of novel agents targeting PDA. Oncolytic viruses represent an emerging class of immunotherapeutic agents that have undergone extensive preclinical investigation and warrant further investigation in well-designed clinical trials...
April 13, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28403812/infections-and-cancer-the-fifty-shades-of-immunity-hypothesis
#7
Camille Jacqueline, Aurélie Tasiemski, Gabriele Sorci, Beata Ujvari, Fatima Maachi, Dorothée Missé, François Renaud, Paul Ewald, Frédéric Thomas, Benjamin Roche
BACKGROUND: Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction. DISCUSSION: Lost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways - from functional aspects to evolutionary considerations such as modernity mismatches - by which infectious organisms could interfere with oncogenic processes through immunity...
April 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28392162/oncolytic-virotherapy-a-contest-between-apples-and-oranges
#8
REVIEW
Stephen J Russell, Kah-Whye Peng
Viruses can be engineered or adapted for selective propagation in neoplastic tissues and further modified for therapeutic transgene expression to enhance their antitumor potency and druggability. Oncolytic viruses (OVs) can be administered locally or intravenously and spread to a variable degree at sites of tumor growth. OV-infected tumor cells die in situ, releasing viral and tumor antigens that are phagocytosed by macrophages, transported to regional lymph nodes, and presented to antigen-reactive T cells, which proliferate before dispersing to kill uninfected tumor cells at distant sites...
April 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28388537/ndv-d90-suppresses-growth-of-gastric-cancer-and-cancer-related-vascularization
#9
Hong Sui, Kaibing Wang, Rui Xie, Xi Li, Kunpeng Li, Yuxian Bai, Xishan Wang, Bin Bai, Dan Chen, Jiazhuang Li, Baozhong Shen
Recent reports suggest promises on using oncolytic Newcastle disease viruses (NDV) to treat different cancers, while the effects of a NDV-D90 strain on gastric cancer remain unknown. Here we showed that NDV-D90 induced gastric cancer cell apoptosis in a dose-dependent manner in 3 gastric cancer cell lines BGC-823, SGC-7901 and MKN-28. Pronounced reduction in cell invasion was detected in NDV-D90-treated BGC-823 and SGC-7901 cells, but not in MKN-28 cells. The increases in cell apoptosis and reduction in cell growth in NDV-D90-treated gastric cancer cells seemingly resulted from augmentation of p38 signaling and suppression of ERK1/2 and Akt signaling...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387388/new-frontiers-in-oncology-immune-checkpoint-inhibitors-in-combination-therapy
#10
G Romano, A Gawlinski
Substantial progress has been achieved in recent years in the field of cancer immunotherapy, with various strategies employed to elicit a host immune response against the tumor. Monoclonal antibodies have been successfully utilized in clinical trials to block key mediators of immune checkpoint pathways, including cytotoxic T-lymphocyte antigen 4, programmed cell death protein 1 and programmed cell death 1 ligand 1. Patients with a range of malignancies have been treated in these clinical trials, and significant benefits were reported among the majority of participants...
February 2017: Drugs of Today
https://www.readbyqxmd.com/read/28376211/rad51-degradation-role-in-oncolytic-virus-poly-adp-ribose-polymerase-inhibitor-combination-therapy-in-glioblastoma
#11
Jianfang Ning, Hiroaki Wakimoto, Cole Peters, Robert L Martuza, Samuel D Rabkin
Background: Clinical success of poly(ADP-ribose) polymerase inhibitors (PARP i ) has been limited to repair-deficient cancers and by resistance. Oncolytic herpes simplex viruses (oHSVs) selectively kill cancer cells, irrespective of mutation, and manipulate DNA damage responses (DDR). Here, we explore potential synthetic lethal-like interactions between oHSV and PARP i . Methods: The efficacy of combining PARP i , oHSV MG18L, and G47Δ in killing patient-derived glioblastoma stem cells (GSCs) was assessed using cell viability assays and Chou-Talalay synergy analysis...
March 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28374246/poxvirus-safety-analysis-in-the-pregnant-mouse-model-vaccinia-and-raccoonpox-viruses
#12
Rachel L Roper
Poxviruses cause many diseases in humans and animals worldwide, and there is a need for vaccines with improved safety and good efficacy. In addition, poxvirus vectors are widely used as recombinant vaccines for various infectious diseases and as recombinant and oncolytic vaccines for cancer. One concern with poxvirus vaccine vectors is that some poxviruses can infect a developing fetus and cause fetal loss or congenital disease. This can be an issue both for patients receiving a vaccine and for pregnant health care providers, including doctors, nurses, and veterinarians, who might receive accidental exposure to the poxvirus by injection or during patient care...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28366525/vaccinia-virus-evasion-of-regulated-cell-death
#13
REVIEW
David L Veyer, Guia Carrara, Carlos Maluquer de Motes, Geoffrey L Smith
Regulated cell death is a powerful anti-viral mechanism capable of aborting the virus replicative cycle and alerting neighbouring cells to the threat of infection. The biological importance of regulated cell death is illustrated by the rich repertoire of host signalling cascades causing cell death and by the multiple strategies exhibited by viruses to block death signal transduction and preserve cell viability. Vaccinia virus (VACV), a poxvirus and the vaccine used to eradicate smallpox, encodes multiple proteins that interfere with apoptotic, necroptotic and pyroptotic signalling...
March 30, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28361224/immunotherapy-for-esophageal-squamous-cell-carcinoma
#14
REVIEW
Takashi Kojima, Toshihiko Doi
Esophageal squamous cell carcinoma have been frustrating to treat, with slow progress made on extending survival. Immunotherapy targeting immune checkpoints, T cells, and infiltrating lymphocytes has shown promise in early studies. The efficacy of pembrolizumab and nivolumab is encouraging. Anti-chemokine receptors and oncolytic viruses are also making headway against these stubborn tumors; improved results when immune checkpoint inhibitors are combined with radiation therapy are eagerly anticipated. Adoptive T cell therapy and vaccines are also under development...
May 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28359239/oncolytic-virotherapy-and-gene-therapy-strategies-for-hepatobiliary-cancers
#15
Takeshi Yamada, Yukako Hamano, Naoyuki Hasegawa, Kazunari K Yokoyama, Ichinosuke Hyodo, Masato Abei
Advanced liver cancers and biliary cancers represent diseases with dismal prognosis because of frequent local invasion and metastasis. Effective therapeutic agents for these cancers have not been established. Oncolytic viruses (OVs) constitute a novel class of promising, selective anticancer agents and recent studies have elucidated their unique features. Moreover, clinical trials are demonstrating promising results. Numerous OVs are being tested in preclinical models of hepatocellular carcinoma (HCC). The lead agent Pexa-Vec (pexastimogene devacirepvec, JX-594) , a recombinant Wyeth strain vaccinia virus, has demonstrated preliminary evidence of safety and efficacy for HCC in clinical trials...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28356525/microrna-mir-27-inhibits-adenovirus-infection-by-suppressing-the-expression-of-snap25-and-txn2
#16
M Machitani, F Sakurai, K Wakabayashi, K Nakatani, M Tachibana, H Mizuguchi
Recent studies have reported that host microRNAs (miRNAs) regulate infection with several types of viruses via various mechanisms, and that inhibition of the miRNA processing factors enhances or prevents viral infection. However, it has not been clarified whether these effects of miRNAs extend to adenovirus (Ad) infection. Here we show that miR-27a/b efficiently inhibit infection with an Ad via the down-regulation of SNAP25 and TXN2, which are members of the SNARE proteins and the thioredoxin family, respectively...
March 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28351167/talimogene-laherparepvec
#17
Patricia A Corrigan, Caroline Beaulieu, Rashmi B Patel, Denise K Lowe
OBJECTIVE: To review the efficacy and safety of talimogene laherparepvec (T-VEC) as well as its pharmacology, pharmacokinetics, drug-drug interactions, handling procedures, cost considerations, and place in therapy. DATA SOURCES: Searches of PubMed (1966 to February 2017) and Cochrane Library (1999 to February 2017) were conducted using the terms talimogene laherparepvec, T-VEC, OncoVEX, immunotherapy, melanoma, and oncolytic virus. Additional information was determined from bibliographies, manufacturer product labeling and website, meeting abstracts, Food and Drug Administration website, and clinicaltrials...
March 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#18
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345027/pre-clinical-assessment-of-c134-a-chimeric-oncolytic-herpes-simplex-virus-in-mice-and-non-human-primates
#19
Kevin A Cassady, David F Bauer, Justin Roth, Melissa R Chambers, Trent Shoeb, Jennifer Coleman, Mark Prichard, G Yancey Gillespie, James M Markert
Oncolytic herpes simplex virus (oHSV) type I constructs are investigational anti-neoplastic agents for a variety of malignancies, including malignant glioma. Clinical trials to date have supported the safety of these agents even when directly administered in the CNS. Traditional pre-clinical US Food and Drug Administration (FDA) toxicity studies for these agents have included the use of two species, generally including murine and primate studies. Recently, the FDA has decreased its requirement of non-human primates as an animal model for ethical reasons, especially for established viral systems where there are good alternative model systems...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28345026/oncolytic-adenoviruses-armed-with-tumor-necrosis-factor-alpha-and-interleukin-2-enable-successful-adoptive-cell-therapy
#20
Riikka Havunen, Mikko Siurala, Suvi Sorsa, Susanna Grönberg-Vähä-Koskela, Michael Behr, Siri Tähtinen, João Manuel Santos, Pauliina Karell, Juuso Rusanen, Dirk M Nettelbeck, Anja Ehrhardt, Anna Kanerva, Akseli Hemminki
Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both...
March 17, 2017: Molecular Therapy Oncolytics
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