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Oncolytic virus and t cells

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https://www.readbyqxmd.com/read/29785403/immunotherapy-for-hepatocellular-carcinoma-current-advances-and-future-expectations
#1
REVIEW
Yingjun Xie, Yien Xiang, Jiyao Sheng, Dan Zhang, Xiaoxiao Yao, Yongsheng Yang, Xuewen Zhang
Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29765544/comparison-of-infectivity-and-spread-between-hsv-1-and-hsv-2-based-oncolytic-viruses-on-tumor-cells-with-different-receptor-expression-profiles
#2
Xinping Fu, Lihua Tao, Pin-Yi Wang, Timothy P Cripe, Xiaoliu Zhang
Herpes simplex virus (HSV) is one of the many viruses that have been modified or adapted for oncolytic purposes. There are two serotypes of HSV, HSV-1 and HSV-2. The majority of oncolytic HSVs, including T-VEC which has recently been approved by the US Food and Drug Administration (FDA) for clinical use in treating late stage melanoma patients, are derived from HSV-1. Recently, we and others have developed several HSV-2 based oncolytic viruses. During our in vitro characterization of oncolytic viruses developed from both serotypes (Baco-1 from HSV-1 and FusOn-H2 from HSV-2), we noticed there is a subpopulation of cancer cells in which both viruses could infect but only FusOn-H2 could spread from cell to cell on monolayers...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764498/talimogene-laherparepvec-combined-with-anti-pd-1-based-immunotherapy-for-unresectable-stage-iii-iv-melanoma-a-case-series
#3
Lillian Sun, Pauline Funchain, Jung Min Song, Patricia Rayman, Charles Tannenbaum, Jennifer Ko, Michael Mcnamara, C Marcela Diaz-Montero, Brian Gastman
BACKGROUND: Talimogene Laherparepvec (T-VEC) is an oncolytic virus approved as an intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action for T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining checkpoint inhibitor therapy with T-VEC injection can lead to improved response rates for stage IIIB-IV melanoma patients. METHODS: We reviewed 10 consecutive cases of stage IIIC to stage IVM1b melanoma patients that received T-VEC plus checkpoint inhibitor(s) therapy (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June 2016 and August 2017 at the Cleveland Clinic with a median follow-up of 7 months (range: 4 to 13 months)...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29743717/integrating-oncolytic-viruses-in-combination-cancer-immunotherapy
#4
REVIEW
Praveen K Bommareddy, Megha Shettigar, Howard L Kaufman
Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancer-immunity cycle. Oncolytic viruses directly lyse tumour cells, leading to the release of soluble antigens, danger signals and type I interferons, which drive antitumour immunity. In addition, some oncolytic viruses can be engineered to express therapeutic genes or can functionally alter tumour-associated endothelial cells, further enhancing T cell recruitment into immune-excluded or immune-deserted tumour microenvironments...
May 9, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29731836/overexpression-of-p53-delivered-using-recombinant-ndv-induces-apoptosis-in-glioma-cells-by-regulating-the-apoptotic-signaling-pathway
#5
Xiaoyong Fan, Hongzhen Lu, Youqiang Cui, Xianzeng Hou, Chuanjiang Huang, Guangcun Liu
Malignant glioma is the most common primary brain carcinoma in the world and has a poor survival rate. Previous studies have demonstrated that p53 dysfunction contributes to the development and severity of malignant glioma. It has also been demonstrated that Newcastle disease virus (NDV) may be a viable candidate for the treatment of various types of cancer. In the present study, a p53 oncolytic agent delivered using recombinant NDV (rNDV-p53) was constructed and its anti-tumor effects in vitro and in vivo were assessed...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29721366/tnfa-and-il-2-armed-adenoviruses-enable-complete-responses-by-anti-pd-1-checkpoint-blockade
#6
V Cervera-Carrascon, M Siurala, J M Santos, R Havunen, S Tähtinen, P Karell, S Sorsa, A Kanerva, A Hemminki
Releasing the patient's immune system against their own malignancy by the use of checkpoint inhibitors is delivering promising results. However, only a subset of patients currently benefit from them. One major limitation of these therapies relates to the inability of T cells to detect or penetrate into the tumor resulting in unresponsiveness to checkpoint inhibition. Virotherapy is an attractive tool for enabling checkpoint inhibitors as viruses are naturally recognized by innate defense elements which draws the attention of the immune system...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29705786/immunotherapy-of-esophageal-cancer-current-status-many-trials-and-innovative-strategies
#7
Maria Alsina, Markus Moehler, Sylvie Lorenzen
The majority of patients with esophageal cancer present with advanced disease and chemotherapy is the mainstay of palliation. However, efficacy is limited by the development of chemotherapy resistance and treatment options beyond first- and second-line treatment are scarce. Immunotherapy is a novel treatment option that has shown encouraging efficacy in several types of cancer, also in esophageal cancer. In esophageal squamous cell cancer (ESCC), early phase evaluation of immune checkpoint inhibitors has yielded promising results, however, results from phase 3 trials are currently still lacking...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29695749/oncolytic-viruses-as-engineering-platforms-for-combination-immunotherapy
#8
REVIEW
Kwame Twumasi-Boateng, Jessica L Pettigrew, Y Y Eunice Kwok, John C Bell, Brad H Nelson
To effectively build on the recent successes of immune checkpoint blockade, adoptive T cell therapy and cancer vaccines, it is critical to rationally design combination strategies that will increase and extend efficacy to a larger proportion of patients. For example, the combination of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and anti-programmed cell death protein 1 (PD1) immune checkpoint inhibitors essentially doubles the response rate in certain patients with metastatic melanoma. However, given the heterogeneity of cancer, it seems likely that even more complex combinations of immunomodulatory agents may be required to obtain consistent, durable therapeutic responses against a broad spectrum of cancers...
April 25, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29599413/combinatorial-effects-of-vegfr-kinase-inhibitor-axitinib-and-oncolytic-virotherapy-in-mouse-and-human-glioblastoma-stem-like-cell-models
#9
Dipongkor Saha, Hiroaki Wakimoto, Cole W Peters, Slawomir J Antoszczyk, Samuel D Rabkin, Robert L Martuza
PURPOSE: Glioblastoma (GBM), a fatal brain cancer, contains a subpopulation of GBM stem-like cells (GSCs) that contribute to resistance to current therapy. Angiogenesis also plays a key role in GBM progression. Therefore, we developed a strategy to target the complex GBM microenvironment, including GSCs and tumor vasculature. EXPERIMENTAL DESIGN: We evaluated the cytotoxic effects of VEFGR tyrosine kinase inhibitor (TKI) axitinib in vitro and then tested anti-tumor efficacy of axitinib in combination with oncolytic herpes simplex virus (oHSV) expressing anti-angiogenic cytokine murine IL12 (G47Δ-mIL12) in two orthotopic GSC-derived GBM models: patientderived recurrent MGG123 GSCs, forming vascular xenografts in immune-deficient mice, and mouse 005 GSCs, forming syngeneic tumors in immune-competent mice...
March 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29588319/improving-car-t-cell-therapy-of-solid-tumors-with-oncolytic-virus-driven-production-of-a-bispecific-t-cell-engager
#10
Anna Wing, Carlos Alberto Fajardo, Avery D Posey, Carolyn Shaw, Tong Da, Regina Young, Ramon Alemany, Carl H June, Sonia Guedan
T cells expressing chimeric antigen receptors (CARTs) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors...
March 27, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29570629/constructing-tc-1-gluc-lmp2-model-tumor-cells-to-evaluate-the-anti-tumor-effects-of-lmp2-related-vaccines
#11
Liying Sun, Yanzhe Hao, Zhan Wang, Yi Zeng
Epstein-Barr virus (EBV) is related to a variety of malignant tumors, and its encoded protein, latent membrane protein 2 (LMP2), is an effective target antigen that is widely used to construct vector vaccines. However, the model cells carrying LMP2 have still not been established to assess the oncolytic effect of LMP2-related vaccines at present. In this study, TC-1-GLUC-LMP2 tumor cells were constructed as target cells to evaluate the anti-tumor effects of LMP2-assosiated vaccines. The results showed that both LMP2 and Gaussia luciferase ( GLuc ) genes could be detected by polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) in TC-1-GLUC-LMP2 cells...
March 23, 2018: Viruses
https://www.readbyqxmd.com/read/29564181/immunotherapy-in-pancreatic-adenocarcinoma-overcoming-barriers-to-response
#12
REVIEW
Ari Rosenberg, Devalingam Mahalingam
Pancreatic adenocarcinoma (PAC) remains one of the leading causes of cancer-related death. Despite multiple advances in targeted and immune therapies, the 5-year survival in advanced PAC remains poor. In this review, we discuss some of the unique aspects of the tumor microenvironment (TME) in PAC that may contribute to its resistance to immune therapies, as well as opportunities to potentially overcome some of these inherent barriers. Furthermore, we discuss strategies to enable immune therapies in PAC such as cytotoxic chemotherapy and radiation therapy, cancer vaccines, cytokine based therapy, oncolytic viruses, and adoptive T-cell therapy...
February 2018: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29561296/potential-clinical-and-immunotherapeutic-utility-of-talimogene-laherparepvec-for-patients-with-melanoma-after-disease-progression-on-immune-checkpoint-inhibitors-and-braf-inhibitors
#13
Jason Chesney, Yoannis Imbert-Fernandez, Sucheta Telang, Mary Baum, Smita Ranjan, Mostafa Fraig, Nicolas Batty
Talimogene laherparepvec is a genetically modified herpes simplex virus type 1-based oncolytic immunotherapy for the local treatment of unresectable subcutaneous and nodal tumors in patients with melanoma recurrent after initial surgery. We report on two patients with melanoma who, after progression on numerous systemic therapies, derived clinical benefit from talimogene laherparepvec in an expanded-access protocol (ClinicalTrials.gov, NCT02147951). Intralesional talimogene laherparepvec (day 1, ≤4 ml 10 PFU/ml; after 3 weeks, ≤4 ml 10 PFU/ml every 2 weeks) was administered until complete response, no injectable tumors, progressive disease, or intolerance occurred...
June 2018: Melanoma Research
https://www.readbyqxmd.com/read/29555782/oncolytic-reovirus-inhibits-immunosuppressive-activity-of-myeloid-derived-suppressor-cells-in-a-tlr3-dependent-manner
#14
Yuki Katayama, Masashi Tachibana, Nozomi Kurisu, Yukako Oya, Yuichi Terasawa, Hiroshi Goda, Kouji Kobiyama, Ken J Ishii, Shizuo Akira, Hiroyuki Mizuguchi, Fuminori Sakurai
Oncolytic reovirus, which possesses 10 segments of dsRNA genome, mediates antitumor effects via not only virus replication in a tumor cell-specific manner, but also activation of antitumor immunity; however, the mechanism(s) of reovirus-induced activation of antitumor immunity have not been fully elucidated. Recent studies have demonstrated that overcoming an immunosuppressive environment in tumor-bearing hosts is important to achieve efficient activation of antitumor immunity. Among the various types of cells involved in immunosuppression, it has been revealed that myeloid-derived suppressor cells (MDSCs) are significantly increased in tumor-bearing hosts and play crucial roles in the immunosuppression in tumor-bearing hosts...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29544689/preclinical-development-of-peptide-vaccination-combined-with-oncolytic-mg1-e6e7-for-hpv-associated-cancer
#15
Matthew J Atherton, Kyle B Stephenson, Jake K Nikota, Qian N Hu, Andrew Nguyen, Yonghong Wan, Brian D Lichty
Human papilloma virus (HPV)-associated cancer is a significant global health burden and despite the presence of viral transforming antigens within neoplastic cells, therapeutic vaccinations are ineffective for advanced disease. HPV positive TC1 cells are susceptible to viral oncolysis by MG1-E6E7, a custom designed oncolytic Maraba virus. Epitope mapping of mice vaccinated with MG1-E6E7 enabled the rational design of synthetic long peptide (SLP) vaccines against HPV16 and HPV18 antigens. SLPs were able to induce specific CD8+ immune responses and the magnitude of these responses significantly increased when boosted by MG1-E6E7...
April 12, 2018: Vaccine
https://www.readbyqxmd.com/read/29504948/pd-l1-in-tumor-microenvironment-mediates-resistance-to-oncolytic-immunotherapy
#16
Dmitriy Zamarin, Jacob M Ricca, Svetlana Sadekova, Anton Oseledchyk, Ying Yu, Wendy M Blumenschein, Jerelyn Wong, Mathieu Gigoux, Taha Merghoub, Jedd D Wolchok
Intralesional therapy with oncolytic viruses (OVs) leads to the activation of local and systemic immune pathways, which may present targets for further combinatorial therapies. Here, we used human tumor histocultures as well as syngeneic tumor models treated with Newcastle disease virus (NDV) to identify a range of immune targets upregulated with OV treatment. Despite tumor infiltration of effector T lymphocytes in response to NDV, there was ongoing inhibition through programmed death ligand 1 (PD-L1), acting as a mechanism of early and late adaptive immune resistance to the type I IFN response and T cell infiltration, respectively...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29474384/development-of-improved-therapeutic-mesothelin-based-vaccines-for-pancreatic-cancer
#17
Michael White, Andrew Freistaedter, Gwendolyn J B Jones, Emmanuel Zervos, Rachel L Roper
Pancreatic cancer is the 5th leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells...
2018: PloS One
https://www.readbyqxmd.com/read/29464075/interleukin-8-activity-influences-the-efficacy-of-adenoviral-oncolytic-immunotherapy-in-cancer-patients
#18
Kristian Taipale, Siri Tähtinen, Riikka Havunen, Anniina Koski, Ilkka Liikanen, Päivi Pakarinen, Riitta Koivisto-Korander, Matti Kankainen, Timo Joensuu, Anna Kanerva, Akseli Hemminki
After the landmark approval of T-VEC, oncolytic viruses are finding their way to the clinics. However, response rates have still room for improvement, and unfortunately there are currently no available markers to predict responses for oncolytic immunotherapy. Interleukin 8 (IL-8) production is upregulated in many cancers and it also connects to several pathways that have been shown to impair the efficacy of adenoviral immunotherapy. We studied the role of IL-8 in 103 cancer patients treated with oncolytic adenoviruses...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29437789/targeted-bite-expression-by-an-oncolytic-vector-augments-therapeutic-efficacy-against-solid-tumors
#19
Tobias Speck, Johannes P W Heidbuechel, Rūta Veinalde, Dirk Jaeger, Christof von Kalle, Claudia R Ball, Guy Ungerechts, Christine E Engeland
Purpose: Immunotherapy with bispecific T-cell engagers has achieved striking success against hematologic malignancies, but efficacy against solid tumors has been limited. We hypothesized that oncolytic measles viruses encoding bispecific T-cell engagers (MV-BiTEs) represent a safe and effective treatment against solid tumors through local BiTE expression, direct tumor cell lysis and in situ tumor vaccination. Experimental Design: To test this hypothesis, we generated MV-BiTEs from the Edmonston B vaccine strain to target two model antigens...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29434366/potentiating-prostate-cancer-immunotherapy-with-oncolytic-viruses
#20
REVIEW
Patrick Lee, Shashi Gujar
The clinical effectiveness of immunotherapies for prostate cancer remains subpar compared with that for other cancers. The goal of most immunotherapies is the activation of immune effectors, such as T cells and natural killer cells, as the presence of these activated mediators positively correlates with patient outcomes. Clinical evidence shows that prostate cancer is immunogenic, accessible to the immune system, and can be targeted by antitumour immune responses. However, owing to the detrimental effects of prostate-cancer-associated immunosuppression, even the newest immunotherapeutic approaches fail to initiate the clinically desired antitumour immune reaction...
April 2018: Nature Reviews. Urology
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