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Virus T cell therapy

Ahmed A Mostafa, Daniel E Meyers, Chandini M Thirukkumaran, Peter J Liu, Kathy Gratton, Jason Spurrell, Qiao Shi, Satbir Thakur, Don G Morris
As the current efficacy of oncolytic viruses (OVs) as monotherapy is limited, exploration of OVs as part of a broader immunotherapeutic treatment strategy for cancer is necessary. Here, we investigated the ability for immune checkpoint blockade to enhance the efficacy of oncolytic reovirus (RV) for the treatment of breast cancer (BrCa). In vitro, oncolysis and cytokine production were assessed in human and murine BrCa cell lines following RV exposure. Furthermore, RV-induced upregulation of tumor cell PD-L1 was evaluated...
June 15, 2018: Cancers
Anna S Griffith, Paul H Hayashi, Lauren Mb Burke, Autumn J McRee
We describe two cases of patients with hepatitis C virus (HCV) treated with direct-acting antiviral (DAA) therapy who had dramatic improvement in hepatocellular carcinoma (HCC) tumor burden with DAA therapy alone. Both patients were diagnosed with HCC on screening magnetic resonance imaging shortly after beginning DAA therapy. Both patients achieved sustained virologic response (SVR) with dramatic improvement in HCC tumor burden on follow-up imaging without HCC treatment. Patients with multifocal or advanced HCC are infrequently treated with antiviral therapy for HCV...
2018: Journal of Hepatocellular Carcinoma
Christine M Calton, Kevin R Kelly, Faiz Anwer, Jennifer S Carew, Steffan T Nawrocki
Although recent treatment advances have improved outcomes for patients with multiple myeloma (MM), the disease frequently becomes refractory to current therapies. MM thus remains incurable for most patients and new therapies are urgently needed. Oncolytic viruses are a promising new class of therapeutics that provide tumor-targeted therapy by specifically infecting and replicating within cancerous cells. Oncolytic therapy yields results from both direct killing of malignant cells and induction of an anti-tumor immune response...
June 14, 2018: Cancers
Liu Yang, Honglang Xie, Zhengzhao Liu, Yinghua Chen, Jinquan Wang, Haitao Zhang, Yongchun Ge, Weixin Hu
BACKGROUND: Severe infections are common complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal involvement. We investigated the clinical characteristics and risk factors of severe infection in Chinese patients with AAV after immunosuppressive therapy. METHODS: A total of 248 patients with a new diagnosis of ANCA-associated vasculitis were included in this study. The incidence, time, site, and risk factors of severe infection by the induction therapies were analysed...
June 14, 2018: BMC Nephrology
Daisuke Watanabe, Fumi Goshima
Oncolytic virotherapy is a kind of antitumor therapy using viruses with natural or engineered tumor-selective replication to intentionally infect and kill tumor cells. An early clinical trial has been performed in the 1950s using wild-type and non-engineered in vitro-passaged virus strains and vaccine strains (first generation oncolytic viruses). Because of the advances in biotechnology and virology, the field of virotherapy has rapidly evolved over the past two decades and innovative recombinant selectivity-enhanced viruses (second generation oncolytic viruses)...
2018: Advances in Experimental Medicine and Biology
Lesley S Park, Janet P Tate, Keith Sigel, Sheldon T Brown, Kristina Crothers, Cynthia Gibert, Matthew Bidwell Goetz, David Rimland, Maria C Rodriguez-Barradas, Roger J Bedimo, Amy C Justice, Robert Dubrow
Background: Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses. Objective: To determine whether viral suppression is associated with decreased cancer risk. Design: Prospective cohort. Setting: Department of Veterans Affairs. Participants: HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015...
June 12, 2018: Annals of Internal Medicine
Jiansong Ji, Qiaoyou Weng, Feng Zhang, Fu Xiong, Yin Jin, Junguo Hui, Jingjing Song, Jun Gao, Minjiang Chen, Qiang Li, David Shin, Xiaoming Yang
Purpose To validate the feasibility and efficacy of intratumoral radiofrequency hyperthermia (RFH)-enhanced herpes simplex virus (HSV) thymidine kinase (TK) and ganciclovir (GCV) (hereafter, HSV-TK/GCV) gene therapy for non-small-cell lung cancer (NSCLC). Materials and Methods This study was performed from November 11, 2015, to April 14, 2017, and included (a) in vitro experiments with human NSCLC cells to establish the proof of principle, (b) in vivo experiments using mice with subcutaneous NSCLC to further demonstrate the principle, and (c) in vivo experiments using rats with orthotopic NSCLC to validate the technical feasibility...
June 12, 2018: Radiology
Torpong Thongngarm, Adhiratha Boonyasiri, Panitan Pradubpongsa, Nattaporn Tesavibul, Tauangtham Anekpuritanang, Piyawut Kreetapirom, Mongkhon Sompornrattanaphan
BACKGROUND: Good syndrome (GS) is an adult-onset immunodeficiency characterized by coexisting thymoma and hypogammaglobulinemia. Clinical course after treatment with intravenous immunoglobulin (IVIg) has rarely been reported. OBJECTIVE: To investigate and report the clinical course and outcomes of GS patients after treatment with IVIg at Thailand's largest national tertiary referral hospital METHODS: This retrospective chart review included patients diagnosed with GS and treated with IVIg during the 1 January 2005 to 31 December 2015 study period...
June 11, 2018: Asian Pacific Journal of Allergy and Immunology
Azam Bolhassani
Acquired immune deficiency syndrome (AIDS) is the most serious stage of human immunodeficiency virus (HIV) infection. The combinatorial anti-retroviral therapy (cART) is widely used in suppressing HIV-1 infection and enhancing life span of infected patients to a significant level. However, delivery of therapeutic molecules is still a major challenge in vivo. The studies showed that the anti-HIV drugs delivered via nano-carriers could be selectively accumulated in infected cells accompanied by low side effects...
June 8, 2018: Current Pharmaceutical Design
Y L Zhang, J L Xie, Y Y Zheng, P Wei, Y H Huang, X D Zheng, X J Teng, W Liu, X G Zhou
Objective: To investigate the clinicopathological features of EBV-positive T/NK cell lymphoproliferative diseases (EBV(+) T/NK-LPD). Methods: The clinical characteristics of 156 cases of EBV(+) T/NK-LPD were collected from August 2002 to March 2015 at Beijing Friendship Hospital, Capital Medical University. Immunohistochemical staining, EBER in situ hybridization and clonal analysis of TCR gene were performed. All patients were followed up. Results: There were 106 male and 50 female patients; patients' age ranged from 1 to 75 years (median 20 years)...
June 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Liam Châtel, Xuefen Yang, François Cholette, Hugo Soudeyns, Paul Sandstrom, Carole Lavigne
Antiretroviral therapy (ART) can lower a patient's HIV plasma viral load to an undetectable level, but following cessation of ART viremia rapidly rebounds. It has been shown that ART does not eliminate latent viruses sequestered into anatomical and cellular reservoirs. Therefore, in patients that have ceased ART, the following rebound in HIV viremia is caused by the activation of latent HIV reservoirs. A major issue in HIV cure research is the quantification of these latent HIV reservoirs. Various reservoir measurement methods exist, but the gold standard technique remains the culture-based quantitative viral outgrowth assay (QVOA)...
June 7, 2018: Archives of Virology
J H Kwon, I A Hanouneh, D Allende, L Yerian, T Diago, B Eghtesad, N N Zein
INTRODUCTION: De novo autoimmune hepatitis, also known as plasma cell hepatitis, is an increasingly recognized entity following liver transplantation. The aim of this study is to investigate the long-term outcomes of patients with de novo autoimmune hepatitis. METHODS: Using transplant liver biopsy database, we identified all patients showing plasma cell hepatitis following liver transplantation between 2008 and 2013. The diagnosis of plasma cell hepatitis was based on the histologic features from liver biopsies...
June 2018: Transplantation Proceedings
Chao-Jiang Gu, Alejandra Borjabad, Eran Hadas, Jennifer Kelschenbach, Boe-Hyun Kim, Wei Chao, Ottavio Arancio, Jin Suh, Bruce Polsky, JoEllyn McMillan, Benson Edagwa, Howard E Gendelman, Mary Jane Potash, David J Volsky
Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI...
June 2018: PLoS Pathogens
Anne-Sophie Kuhlmann, Christopher W Peterson, Hans-Peter Kiem
PURPOSE OF REVIEW: Combination antiretroviral therapy (ART) has enabled tremendous progress in suppressing HIV replication in infected patients. However, ART alone cannot eradicate HIV and its latent, persisting reservoirs. Novel approaches are needed to eradicate the virus or achieve functional cure in the absence of ART. RECENT FINDINGS: Adoptive T-cell therapies were initially tested in HIV-infected individuals with limited efficiency. Benefiting from new and improved methodologies, an increasing array of CAR T-cell therapies has been successfully developed in the cancer immunotherapy field, demonstrating promising new avenues that could be applied to HIV...
June 6, 2018: Current Opinion in HIV and AIDS
Robin A Buerki, Zinal S Chheda, Hideho Okada
The field of cancer immunotherapy has made exciting progress for some cancer types in recent years. However, recent failures of late phase clinical trials evaluating checkpoint blockade in glioblastoma (GBM) patients represent continued challenges for brain cancer immunotherapy. This is likely due to multiple factors, including but not limited to marked genetic and antigenic heterogeneity, relatively low mutational loads and paucity of GBM-infiltrating T cells. We review recent and ongoing studies targeting the checkpoint molecules as monotherapy or in combination with other modalities, and discuss the mechanisms underlying the unresponsiveness of GBM to single modality immunotherapy approaches...
June 5, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
S D Hwang, J H Lee, S W Lee, J K Kim, M-J Kim, J H Song
BACKGROUND: Reactivation of BK polyomavirus causes destructive virus allograft nephropathy; however, treatment options are limited. Herein, we report a case in which a patient with T cell-mediated rejection was treated with steroid therapy. The patient subsequently developed BK viremia and was successfully treated by using intravenous immunoglobulin (IVIG) after failing to respond to conventional treatment. CASE PRESENTATION: A 54-year-old man had been undergoing peritoneal dialysis for 3 years before kidney transplantation...
June 2, 2018: Transplantation Proceedings
Lei Dou, Yoshihiro Ono, Yi-Fa Chen, Angus W Thomson, Xiao-Ping Chen
The unique liver immune microenvironment favors resistance to inflammation that promotes normal physiological function. At the same time, it endows the liver with tolerogenic properties that may promote pathological processes. Hepatic dendritic cells (HDCs) initiate and orchestrate immune responses depending on signals they receive from the local environment and are thought to contribute to liver tolerance. Thus, HDCs facilitate impaired T cell responses that are observed in persistent hepatitis C virus (HCV) infection, hepatocellular carcinoma progression, and liver allograft transplantation...
May 2018: Seminars in Liver Disease
Rachael Watson Levings, Ted A Broome, Andrew D Smith, Brett L Rice, Eric P Gibbs, D Alex Myara, E Viktoria Hyddmark, Elham Nasri, Ali Zarezadeh, Padraic P Levings, Yuan Lu, E Anthony Dacanay, Gregory B Foremny, Christopher H Evans, Alison J Morton, Mathew Winter, Michael J Dark, David M Nickerson, Patrick T Colahan, Steven Craig Ghivizzani
142: Toward the treatment of osteoarthritis (OA), we have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of gene products with therapeutic potential. As OA frequently affects weight-bearing joints, we performed pharmacokinetic studies in the equine forelimb to identify parameters of scAAV gene delivery relevant to clinical translation. Using the coding sequence for interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter we first generated an scAAV vector containing an optimized cDNA for equine IL-1Ra...
June 5, 2018: Human Gene Therapy. Clinical Development
Adrienne E Swanstrom, Robert J Gorelick, Guoxin Wu, Bonnie Howell, Anitha Vijayagopalan, Rebecca Shoemaker, Kelli Oswald, Siddhartha A Datta, Brandon Keele, Gregory Del Prete, Elena Chertova, Julian Bess, Jeffrey Lifson
Although effective at suppressing viral replication, combination antiretroviral treatment (cART) does not represent definitive therapy of HIV infection due to persistence of replication-competent viral reservoirs. The advent of effective cART regimens for simian immunodeficiency virus (SIV) infected nonhuman primates (NHP) has enabled the development of relevant models for studying viral reservoirs and intervention strategies targeting them. Viral reservoir measurements are crucial for such studies, but are problematic...
June 5, 2018: AIDS Research and Human Retroviruses
Francesca Marino-Merlo, Antonio Mastino, Sandro Grelli, Olivier Hermine, Ali Bazarbachi, Beatrice Macchi
Human T cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia/lymphoma (ATL), HTLV-1 associated myelopathy (HAM/TSP), and of a number of inflammatory diseases with an estimated 10-20 million infected individuals worldwide. Despite a number of therapeutic approaches, a cure for ATL is still in its infancy. Conventional chemotherapy has short-term efficacy, particularly in the acute subtype. Allogeneic stem cell transplantation offers long-term disease control to around one third of transplanted patients, but few can reach to transplant...
2018: Frontiers in Microbiology
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