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Oncolytic virus and t cells

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https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#1
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28902983/solid-tumor-immunotherapy-with-t-cell-engager-armed-oncolytic-viruses
#2
REVIEW
Eleanor M Scott, Margaret R Duffy, Joshua D Freedman, Kerry D Fisher, Leonard W Seymour
Oncolytic viruses (OVs) are novel anticancer agents that combine direct cancer cell killing with the stimulation of antitumor immunity. In addition, OVs can be engineered to deliver biological therapeutics directly to tumors, offering unique opportunities to design multimodal anticancer strategies. Here, a case for arming OVs with bispecific T cell engagers (BiTEs) is put forward. BiTEs redirect the cytotoxicity of polyclonal T cells to target cells of choice, and have demonstrated efficacy against a number of hematological cancers...
September 13, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28875159/myxoma-virus-optimizes-cisplatin-for-the-treatment-of-ovarian-cancer-in%C3%A2-vitro-and-in-a-syngeneic-murine-dissemination-model
#3
Bernice Nounamo, Jason Liem, Martin Cannon, Jia Liu
A therapeutic approach to improve treatment outcome of ovarian cancer (OC) in patients is urgently needed. Myxoma virus (MYXV) is a candidate oncolytic virus that infects to eliminate OC cells. We found that in vitro MYXV treatment enhances cisplatin or gemcitabine treatment by allowing lower doses than the corresponding IC50 calculated for primary OC cells. MYXV also affected OC patient ascites-associated CD14(+) myeloid cells, one of the most abundant immunological components of the OC tumor environment; without causing cell death, MYXV infection reduces the ability of these cells to secrete cytokines such as IL-10 that are signatures of the immunosuppressive tumor environment...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28870120/virotherapy-research-in-germany-from-engineering-to-translation-a-review-as-contribution-to-the-combined-annual-meeting-of-the-german-and-european-societies-of-gene-and-cell-therapy-2017
#4
Guy Ungerechts, Christine E Engeland, Christian J Buchholz, Jürgen Eberle, Henry Fechner, Karsten Geletneky, Per Sonne Holm, Florian Kreppel, Florian Kühnel, Karl Sebastian Lang, Mathias F Leber, Antonio Marchini, Markus Moehler, Michael D Mühlebach, Jean Rommelaere, Christoph Springfeld, Ulrich M Lauer, Dirk M Nettelbeck
Virotherapy is a unique modality for treatment of cancer with oncolytic viruses (OVs) that selectively infect and lyse tumor cells, spread within tumors, and activate anti-tumor immunity. Different viruses are being developed as OVs preclinically and clinically, several of them engineered to encode therapeutic proteins for tumor-targeted gene therapy. Scientists and clinicians in Germany have made significant contributions to OV research and development, which are highlighted in this review article. Innovative strategies for "shielding", entry- or post-entry targeting, and "arming" of OVs have been established focusing on adeno-, measles, parvo-, and vaccinia virus platforms...
September 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28857157/newcastle-disease-virus-mediates-pancreatic-tumor-rejection-via-nk-cell-activation-and-prevents-cancer-relapse-by-prompting-adaptive-immunity
#5
Theresa Schwaiger, Michael R Knittler, Christian Grund, Angela Roemer-Oberdoerfer, Joachim-Friedrich Kapp, Markus M Lerch, Thomas C Mettenleiter, Julia Mayerle, Ulrike Blohm
Pancreatic cancer is the 8(th) most common cause of cancer-related deaths worldwide and the tumor with the poorest prognosis of all solid malignancies. In 1957 it was discovered that Newcastle disease virus (NDV) has oncolytic properties on tumor cells. To study the oncolytic properties of NDV in pancreatic cancer a single dose was administered intravenously in a syngenic orthotopic tumor model employing two different murine pancreatic adenocarcinoma cell lines (DT6606PDA, Panc02). Tumor growth was monitored and immune response was analyzed...
August 31, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28856238/reovirus-fast-protein-enhances-vesicular-stomatitis-virus-oncolytic-virotherapy-in-primary-and-metastatic-tumor-models
#6
Fabrice Le Boeuf, Simon Gebremeskel, Nichole McMullen, Han He, Anna L Greenshields, David W Hoskin, John C Bell, Brent Johnston, Chungen Pan, Roy Duncan
The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral fusogens (∼100-150 amino acids) and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant) encoding the p14 FAST protein (VSV-p14) was compared with a similar construct encoding GFP (VSV-GFP) in cell culture and syngeneic BALB/c tumor models...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28839138/smac-mimetics-and-oncolytic-viruses-synergize-in-driving-anticancer-t-cell-responses-through-complementary-mechanisms
#7
Dae-Sun Kim, Himika Dastidar, Chunfen Zhang, Franz J Zemp, Keith Lau, Matthias Ernst, Andrea Rakic, Saif Sikdar, Jahanara Rajwani, Victor Naumenko, Dale R Balce, Ben W Ewanchuk, Pankaj Taylor, Robin M Yates, Craig Jenne, Chris Gafuik, Douglas J Mahoney
Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound and oncolytic virus therapies also modulate host immune responses in ways we hypothesized would complement one another in promoting anticancer T-cell immunity. We show that Smac-mimetic compound and oncolytic virus therapies synergize in driving CD8(+) T-cell responses toward tumors through distinct activities. Smac-mimetic compound treatment with LCL161 reinvigorates exhausted CD8(+) T cells within immunosuppressed tumors by targeting tumor-associated macrophages for M1-like polarization...
August 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28810147/macrophage-polarization-contributes-to-glioblastoma-eradication-by-combination-immunovirotherapy-and-immune-checkpoint-blockade
#8
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/28791656/egfr-as-a-target-for-glioblastoma-treatment-an-unfulfilled-promise
#9
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/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#10
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/28751892/sharpening-the-edge-for-precision-cancer-immunotherapy-targeting-tumor-antigens-through-oncolytic-vaccines
#11
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/28749907/immunotherapy-in-urothelial-cancer-part-1-t-cell-checkpoint-inhibition-in-advanced-or-metastatic-disease
#12
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/28710334/stem-cell-released-oncolytic-herpes-simplex-virus-has-therapeutic-efficacy-in-brain-metastatic-melanomas
#13
Wanlu Du, Ivan Seah, Oumaima Bougazzoul, GiHun Choi, Katrina Meeth, Marcus W Bosenberg, Hiroaki Wakimoto, David Fisher, Khalid Shah
The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs)...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28706012/local-delivery-of-oncovex-mgm-csf-generates-systemic-anti-tumor-immune-responses-enhanced-by-cytotoxic-t-lymphocyte-associated-protein-blockade
#14
Achim K Moesta, Keegan Cooke, Julia Piasecki, Petia Mitchell, James B Rottman, Karen Fitzgerald, Jinghui Zhan, Becky Yang, Tiep Le, Brian Belmontes, Oluwatayo F Ikotun, Kim Merriam, Charles Glaus, Kenneth Ganley, David H Cordover, Andrea M Boden, Rafael Ponce, Courtney Beers, Pedro J Beltran
Talimogene laherparepvec, a new oncolytic immunotherapy, has been recently approved for the treatment of melanoma. Using a murine version of the virus we characterized local and systemic anti-tumor immune responses driving efficacy in murine syngeneic models.<br /><br />Experimental Design: The activity of talimogene laherparepvec was characterized against melanoma cell lines using an in vitro viability assay. Efficacy of OncoVEX(mGM-CSF) (talimogene laherparepvec with the mouse granulocyte-macrophage colony-stimulating factor transgene) alone or in combination with checkpoint blockade was characterized in A20 and CT-26 contralateral murine tumor models...
July 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28678032/therapeutic-oncolytic-viruses-clinical-advances-and-future-directions
#15
Susanne G Warner, Michael P O'Leary, Yuman Fong
PURPOSE OF REVIEW: The present review will highlight recent advances in the clinical application of oncolytic viral therapy. RECENT FINDINGS: Until recently, oncolytic viral researchers saw the immune system as an enemy that would clear the virus from the bloodstream. However, researchers now understand that sustained responses are seen in those patients with more robust antitumor immune responses. Much of the current focus in oncolytic viral research is trained on manipulation of the immune system to affect cancer cell killing in the tumor microenvironment and to facilitate durable systemic antitumor immunity...
September 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28669340/oncolytic-tanapoxvirus-expressing-interleukin-2-is-capable-of-inducing-the-regression-of-human-melanoma-tumors-in-the-absence-of-t-cells
#16
Tiantian Zhang, Dennis H Kordish, Yogesh R Suryawanshi, Rob R Eversole, Steven Kohler, Charles D Mackenzie, Karim Essani
Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-2 (IL-2), a T-cell growth factor, plays a critical role in activating T cells, natural killer (NK) cells and macrophages in both the innate and adaptive immune system. In this study, a recombinant TANV expressing mouse IL-2 (TANVΔ66R/mIL-2) was generated, where the viral thymidine kinase (TK) gene (66R) was replaced with the mIL-2 transgene...
June 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28651743/the-combination-of-nk-and-cd8-t-cells-with-ccl20-il15-armed-oncolytic-adenoviruses-enhances-the-growth-suppression-of-tert-positive-tumor-cells
#17
Jun-Feng Ye, Wen-Xi Qi, Ming-Yuan Liu, Yang Li
Adoptive immunotherapy and targeted gene therapy have been extensively used to eliminate tumor cells. The combination treatment is capable of efficiently generating an effective antitumor immune response and disrupting tumor-induced tolerance. Moreover, effective antitumor immune responses are dependent on coordinate interaction among various effector cells. This study focused on whether the combination of cytotoxic effector cell-based adoptive immunotherapy and CCL20/IL15-armed oncolytic adenoviruses could induce enhanced antitumor activity...
August 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28650343/anthrax-toxin-receptor-1-is-the-cellular-receptor-for-seneca-valley-virus
#18
Linde A Miles, Laura N Burga, Eric E Gardner, Mihnea Bostina, John T Poirier, Charles M Rudin
Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. It has shown promise as a cancer therapeutic in preclinical studies and early-phase clinical trials. Here, we have identified anthrax toxin receptor 1 (ANTXR1) as the receptor for SVV using genome-wide loss-of-function screens. ANTXR1 is necessary for permissivity in vitro and in vivo. However, robust SVV replication requires an additional innate immune defect. We found that SVV interacts directly and specifically with ANTXR1, that this interaction is required for SVV binding to permissive cells, and that ANTXR1 expression is necessary and sufficient for infection in cell lines with decreased expression of antiviral IFN genes at baseline...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#19
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#20
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
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