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Oncolytic virus and t cells

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https://www.readbyqxmd.com/read/28710334/stem-cell-released-oncolytic-herpes-simplex-virus-has-therapeutic-efficacy-in-brain-metastatic-melanomas
#1
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 14, 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
#2
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
#3
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...
July 3, 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
#4
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
#5
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...
June 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28650343/anthrax-toxin-receptor-1-is-the-cellular-receptor-for-seneca-valley-virus
#6
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...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#7
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
#8
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
https://www.readbyqxmd.com/read/28634161/oncolytic-adenovirus-expressing-bispecific-antibody-targets-t-cell-cytotoxicity-in-cancer-biopsies
#9
Joshua D Freedman, Joachim Hagel, Eleanor M Scott, Ioannis Psallidas, Avinash Gupta, Laura Spiers, Paul Miller, Nikolaos Kanellakis, Rebecca Ashfield, Kerry D Fisher, Margaret R Duffy, Leonard W Seymour
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single-chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T-cell engager (BiTE) binds to EpCAM on target cells and cross-links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication...
June 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28611307/review-oncolytic-virotherapy-updates-and-future-directions
#10
REVIEW
Christos Fountzilas, Sukeshi Patel, Devalingam Mahalingam
Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or non-resectable melanoma...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28594388/gene-therapy-for-pancreatic-cancer-specificity-issues-and-hopes
#11
REVIEW
Marie Rouanet, Marine Lebrin, Fabian Gross, Barbara Bournet, Pierre Cordelier, Louis Buscail
A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes)...
June 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28589085/immune-system-friend-or-foe-of-oncolytic-virotherapy
#12
REVIEW
Anna C Filley, Mahua Dey
Oncolytic viruses (OVs) are an emerging class of targeted anticancer therapies designed to selectively infect, replicate in, and lyse malignant cells without causing harm to normal, healthy tissues. In addition to direct oncolytic activity, OVs have shown dual promise as immunotherapeutic agents. The presence of viral infection and subsequently generated immunogenic tumor cell death trigger innate and adaptive immune responses that mediate further tumor destruction. However, antiviral immune responses can intrinsically limit OV infection, spread, and overall therapeutic efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28578991/oncolytic-vsv-primes-differential-responses-to-immuno-oncology-therapy
#13
Nicholas M Durham, Kathy Mulgrew, Kelly McGlinchey, Noel R Monks, Hong Ji, Ronald Herbst, JoAnn Suzich, Scott A Hammond, Elizabeth J Kelly
Vesicular stomatitis virus encoding the IFNβ transgene (VSV-IFNβ) is a mediator of potent oncolytic activity and is undergoing clinical evaluation for the treatment of solid tumors. Emerging preclinical and clinical data suggest treatment of tumors with oncolytic viruses may sensitize tumors to checkpoint inhibitors and increase the anti-tumor immune response. New generations of immuno-oncology molecules including T cell agonists are entering clinical development and could be hypothesized to enhance the activity of oncolytic viruses, including VSV-IFNβ...
June 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28578522/evaluation-of-the-oncolytic-potential-of-r2b-mukteshwar-vaccine-strain-of-newcastle-disease-virus-ndv-in-a-colon-cancer-cell-line-sw-620
#14
Kishan K Sharma, Irsadullakhan H Kalyani, Jogeswar Mohapatra, Satish D Patel, Dharmesh R Patel, Priti D Vihol, Abhijit Chatterjee, Dinesh R Patel, Bhavesh Vyas
Virotherapy is emerging as an alternative treatment of cancer. Among the candidate oncolytic viruses (OVs), Newcastle disease virus (NDV) has emerged as a promising non-engineered OV. In the present communication, we explored the oncolytic potential of R2B Mukteshwar strain of NDV using SW-620 colon cancer cells. SW-620 cells were xenografted in nude mice and after evaluation of the safety profile, 1 x 10(7) plaque forming units (PFU) of NDV were inoculated as virotherapeutic agent via the intratumoral (I/T) and intravenous (I/V) route...
June 3, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28566332/oncolytic-adenovirus-and-tumor-targeting-immune-modulatory-therapy-improve-autologous-cancer-vaccination
#15
Hong Jiang, Yisel Rivera-Molina, Candelaria Gomez-Manzano, Karen Clise-Dwyer, Laura Bover, Luis M Vence, Ying Yuan, Frederick F Lang, Carlo Toniatti, Mohammad B Hossain, Juan Fueyo
Oncolytic viruses selectively lyse tumor cells, disrupt immunosuppression within the tumor, and reactivate antitumor immunity, but they have yet to live up to their therapeutic potential. Immune checkpoint modulation has been efficacious in a variety of cancer with an immunogenic microenvironment, but is associated with toxicity due to nonspecific T-cell activation. Therefore, combining these two strategies would likely result in both effective and specific cancer therapy. To test the hypothesis, we first constructed oncolytic adenovirus Delta-24-RGDOX expressing the immune costimulator OX40 ligand (OX40L)...
July 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28555136/oncolytic-immunotherapy-conceptual-evolution-current-strategies-and-future-perspectives
#16
REVIEW
Zong Sheng Guo, Zuqiang Liu, Stacy Kowalsky, Mathilde Feist, Pawel Kalinski, Binfeng Lu, Walter J Storkus, David L Bartlett
The concept of oncolytic virus (OV)-mediated cancer therapy has been shifted from an operational virotherapy paradigm to an immunotherapy. OVs often induce immunogenic cell death (ICD) of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. We and others have developed a number of strategies to further stimulate antitumor immunity and to productively modulate the tumor microenvironment (TME) for potent and sustained antitumor immune cell activity. First, OVs have been engineered or combined with other ICD inducers to promote more effective T cell cross-priming, and in many cases, the breaking of functional immune tolerance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28553616/the-oncolytic-virotherapy-era-in-cancer-management-prospects-of-applying-h-1-parvovirus-to-treat-blood-and-solid-cancers
#17
Assia L Angelova, Mathias Witzens-Harig, Angel S Galabov, Jean Rommelaere
Non-Hodgkin lymphoma (NHL) and leukemia are among the most common cancers worldwide. While the treatment of NHL/leukemia of B-cell origin has much progressed with the introduction of targeted therapies, few treatment standards have been established for T-NHL/leukemia. As presentation in both B- and T-NHL/leukemia patients is often aggressive and as prognosis for relapsed disease is especially dismal, this cancer entity poses major challenges and requires innovative therapeutic approaches. In clinical trials, oncolytic viruses (OVs) have been used against refractory multiple myeloma (MM)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28539588/cooperation-of-oncolytic-herpes-virotherapy-and-pd-1-blockade-in-murine-rhabdomyosarcoma-models
#18
Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M Swain, Julia K Love, Joseph R Stanek, Louis Boon, Joe Conner, Timothy P Cripe
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536345/viroimmunotherapy-of-thoracic-cancers
#19
REVIEW
Alexander S Dash, Manish R Patel
Thoracic cancers, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and malignant pleural mesothelioma (MM), cause the highest rate of cancer mortality worldwide. Most of these deaths are as a result of NSCLC; however, prognoses for the other two diseases remain as some of the poorest of any cancers. Recent advances in immunotherapy, specifically immune checkpoint inhibitors, have begun to help a small population of patients with advanced lung cancer. People who respond to these immune therapies generally have a durable response and many see dramatic decreases in their disease...
January 4, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536305/shaping-the-tumor-stroma-and-sparking-immune-activation-by-cd40-and-4-1bb-signaling-induced-by-an-armed-oncolytic-virus
#20
Emma Eriksson, Ioanna Milenova, Jessica Wenthe, Magnus Ståhle, Justyna Leja-Jarblad, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Angelica Loskog
PURPOSE: Pancreatic cancer is a severe indication with short expected survival despite surgery and/or combination chemotherapeutics. Checkpoint blockade antibodies are approved for several cancer indications but pancreatic cancer has remained refractory. However, there are clinical data suggesting that stimulation of the CD40 pathway may be of interest for these patients. Oncolytic viruses armed with immunostimulatory genes represent an interesting approach. Herein we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activate the CD40 and 4-1BB pathways, respectively...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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