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https://www.readbyqxmd.com/read/29243498/-cart-intensification-by-the-hiv-1-tat-b-clade-vaccine-progress-to-phase-iii-efficacy-studies
#1
Aurelio Cafaro, Cecilia Sgadari, Orietta Picconi, Antonella Tripiciano, Sonia Moretti, Vittorio Francavilla, Maria Rosaria Pavone Cossut, Stefano Buttò, Giovanni Cozzone, Fabrizio Ensoli, Paolo Monini, Barbara Ensoli
In spite of its success at suppressing HIV replication, combination antiretroviral therapy (cART) only partially reduces immune dysregulation and loss of immune functions. These cART-unmet needs appear to be due to persistent virus replication and cell-to-cell transmission in reservoirs, and are causes of increased patients' morbidity and mortality. Up to now, therapeutic interventions aimed at cART-intensification by attacking the virus reservoir have failed. Areas covered: We briefly review the rationale and clinical development of Tat therapeutic vaccine in cART-treated subjects in Italy and South Africa (SA)...
December 15, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29242243/an-infrared-dye-conjugated-virus-like-particle-for-the-treatment-of-primary-uveal-melanoma
#2
Rhonda C Kines, Isabella Varsavsky, Sanghamitra Choudhary, Debaditya Bhattacharya, Sean Spring, Roger J McLaughlin, Shin J Kang, Hans E Grossniklaus, Demitrios G Vavvas, Stephen Monks, John R MacDougall, Elisabet de Los Pinos, John T Schiller
The work outlined herein describes AU-011, a novel recombinant papillomavirus-like particle (VLP) drug conjugate and its initial evaluation as a potential treatment for primary uveal melanoma. The VLP is conjugated with a phthalocyanine photosensitizer, IRDye 700DX, that exerts its cytotoxic effect through photo-activation with a near-infrared laser. We assessed the anti-cancer properties of AU-011 in vitro utilizing a panel of human cancer cell lines and in vivo using murine subcutaneous and rabbit orthotopic xenograft models of uveal melanoma...
December 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29239916/early-experience-with-clinimacs-prodigy-ccs-ifn-gamma-system-in-selection-of-virus-specific-t-cells-from-third-party-donors-for-pediatric-patients-with-severe-viral-infections-after-hematopoietic-stem-cell-transplantation
#3
Krisztián Kállay, Csaba Kassa, Marienn Réti, Éva Karászi, János Sinkó, Vera Goda, Anita Stréhn, Katalin Csordás, Orsolya Horváth, Attila Szederjesi, Szabolcs Tasnády, Apor Hardi, Gergely Kriván
Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases...
December 12, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29235226/reduced-therapeutic-effect-of-antiviral-drugs-in-patients-with-hepatitis-b-virus-reactivation-after-hematopoietic-stem-cell-transplantation
#4
Masamichi Kimura, Koji Nishikawa, Hisashi Sakamaki, Masashi Mizokami, Kiminori Kimura
BACKGROUND: Patients with resolved Hepatitis B virus (HBV) infection following hematopoietic stem cell transplantation (HSCT) are potentially at high risk of HBV reactivation. Although anti-viral drug therapy is recommended when HBV DNA reappears in the serum, drug efficacy after HBV reactivation remains unclear. METHODS: Host immune response against HBV was investigated via immunological analyses at 12 months after entecavir (ETV) treatment in six HSCT-treated and five non-HSCT-treated patients with HBV reactivation, and 18 patients with chronic hepatitis B (CHB)...
December 13, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29229308/lymphocyte-dominant-encephalitis-and-meningitis-in-simian-immunodeficiency-virus-infected-macaques-receiving-antiretroviral-therapy
#5
Lisa M Mangus, Sarah E Beck, Suzanne E Queen, Samuel A Brill, Erin N Shirk, Kelly A Metcalf Pate, Dillon C Muth, Robert J Adams, Lucio Gama, Janice E Clements, Joseph L Mankowski
A retrospective neuropathologic review of 30 SIV-infected pigtailed macaques receiving combination antiretroviral therapy (cART) was conducted. Seventeen animals with lymphocyte-dominant inflammation in the brain and/or meninges that clearly was morphologically distinct from prototypic SIV encephalitis and human immunodeficiency virus encephalitis were identified. Central nervous system (CNS) infiltrates in cART-treated macaques primarily comprised CD20+ B cells and CD3+ T cells with fewer CD68+ macrophages...
December 5, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29222166/effect-of-il-7-therapy-on-phospho-ribosomal-protein-s6-and-traf1-expression-in-hiv-specific-cd8-t-cells-in-patients-receiving-antiretroviral-therapy
#6
Chao Wang, Maria I Edilova, Lisa E Wagar, Shariq Mujib, Meromit Singer, Nicole F Bernard, Thérèse Croughs, Michael M Lederman, Irini Sereti, Margaret A Fischl, Elisabeth Kremmer, Mario Ostrowski, Jean-Pierre Routy, Tania H Watts
IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice...
December 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29221181/analysis-of-ctcl-cell-lines-reveals-important-differences-between-mycosis-fungoides-s%C3%A3-zary-syndrome-vs-htlv-1-leukemic-cell-lines
#7
Elena Netchiporouk, Jennifer Gantchev, Matthew Tsang, Philippe Thibault, Andrew K Watters, John-Douglas Matthew Hughes, Feras M Ghazawi, Anders Woetmann, Niels Ødum, Denis Sasseville, Ivan V Litvinov
HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#8
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29217527/merkel-cell-carcinoma-in-the-age-of-immunotherapy-facts-and%C3%A2-hopes
#9
Aric Colunga, Thomas Pulliam, Paul Nghiem
Merkel cell carcinoma (MCC) is a rare (~2,000 US cases/year) but aggressive neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only infrequently (<10% of cases) offers durable clinical responses (>1 year) suggesting a great need for improved therapeutic options. In 2008, the Merkel cell polyomavirus (MCPyV) was discovered and is clonally integrated in ~80% of MCC tumors. The remaining 20% of MCC tumors have large numbers of UV-associated mutations. Importantly, both the UV-induced-neoantigens in virus-negative tumors and the MCPyV T antigen oncogenes that are required for virus-positive tumor growth are immunogenic...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#10
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29213157/immunotherapy-and-gene-therapy-as-novel-treatments-for-cancer
#11
REVIEW
Martha Montserrat Rangel-Sosa, Estuardo Aguilar-Córdova, Augusto Rojas-Martínez
The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma...
September 30, 2017: Colombia Médica: CM
https://www.readbyqxmd.com/read/29212930/control-of-htlv-1-infection-by-eliminating-envelope-protein-positive-cells-with-recombinant-vesicular-stomatitis-viruses-encoding-htlv-1-primary-receptor
#12
Kenta Tezuka, Kazu Okuma, Madoka Kuramitsu, Sahoko Matsuoka, Reiko Tanaka, Yuetsu Tanaka, Isao Hamaguchi
Human T-cell leukemia virus type 1 (HTLV-1) infection causes adult T-cell leukemia (ATL), which is frequently resistant to current available therapies and has a very poor prognosis. To prevent the development of ATL among carriers it is important to control HTLV-1-infected cells in infected individuals. Therefore, the establishment of novel therapies with drugs specifically targeting infected cells is urgently required. This study aimed to develop a potential therapy by generating recombinant vesicular stomatitis viruses (rVSVs) that lack an envelope glycoprotein G and instead encode HTLV-1 receptor(s) with human glucose transporter 1 (GLUT1), neuropilin 1 (NRP1), or heparan sulfate proteoglycans (HSPGs) including syndecan 1 (SDC1), designated as VSVΔG-GL, VSVΔG-NP, or VSVΔG-SD, respectively...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212866/acquired-haemophilia-a-complicating-alemtuzumab-therapy-for-multiple-sclerosis
#13
Georgia McCaughan, Jennifer Massey, Ian Sutton, Jennifer Curnow
Alemtuzumab is a highly efficacious therapy used in the treatment of multiple sclerosis (MS), but uncoupling of T and B cell repopulation during immune reconstitution associates with an increasing range of secondary B cell-mediated autoimmune complications. A 34-year-old woman developed Graves' disease 11 months following an initial course of alemtuzumab treatment for MS. Nine months following the second treatment with alemtuzumab, the patient presented with spontaneous intramuscular and subcutaneous haemorrhage due to development of an inhibitory autoantibody to coagulation factor VIII...
December 5, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29212716/a-randomized-controlled-safety-efficacy-trial-of-therapeutic-vaccination-in-hiv-infected-individuals-who-initiated-antiretroviral-therapy-early-in-infection
#14
Michael C Sneller, J Shawn Justement, Kathleen R Gittens, Mary E Petrone, Katherine E Clarridge, Michael A Proschan, Richard Kwan, Victoria Shi, Jana Blazkova, Eric W Refsland, Daryl E Morris, Kristen W Cohen, M Juliana McElrath, Rong Xu, Michael A Egan, John H Eldridge, Erika Benko, Colin Kovacs, Susan Moir, Tae-Wook Chun, Anthony S Fauci
Despite substantial clinical benefits, complete eradication of HIV has not been possible using antiretroviral therapy (ART) alone. Strategies that can either eliminate persistent viral reservoirs or boost host immunity to prevent rebound of virus from these reservoirs after discontinuation of ART are needed; one possibility is therapeutic vaccination. We report the results of a randomized, placebo-controlled trial of a therapeutic vaccine regimen in patients in whom ART was initiated during the early stage of HIV infection and whose immune system was anticipated to be relatively intact...
December 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29209782/advances-in-immunotherapeutic-research-for-glioma-therapy
#15
REVIEW
Jeremy Tetsuo Miyauchi, Stella E Tsirka
Gliomas are primary malignancies of the brain. Tumors are staged based on malignancy, nuclear atypia, and infiltration of the surrounding brain parenchyma. Tumors are often diagnosed once patients become symptomatic, at which time the lesion is sizable. Glioblastoma (grade IV glioma) is highly aggressive and difficult to treat. Most tumors are diagnosed de novo. The gold standard of therapy, implemented over a decade ago, consists of fractionated radiotherapy and temozolomide, but unfortunately, chemotherapeutic resistance arises...
December 5, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/29206656/hiv-integration-sites-and-implications-for-maintenance-of-the-reservoir
#16
Jori Symons, Paul U Cameron, Sharon R Lewin
PURPOSE OF REVIEW: To provide an overview of recent research of how HIV integration relates to productive and latent infection and implications for cure strategies. RECENT FINDINGS: How and where HIV integrates provides new insights into how HIV persists on antiretroviral therapy (ART). Clonal expansion of infected cells with the same integration site demonstrates that T-cell proliferation is an important factor in HIV persistence, however, the driver of proliferation remains unclear...
December 4, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29203150/retroviral-and-lentiviral-safety-analysis-of-gene-modified-t-cell-products-and-infused-hiv-and-oncology-patients
#17
Katherine T Marcucci, Julie K Jadlowsky, Wei-Ting Hwang, Megan Suhoski-Davis, Vanessa E Gonzalez, Irina Kulikovskaya, Minnal Gupta, Simon F Lacey, Gabriela Plesa, Anne Chew, J Joseph Melenhorst, Bruce L Levine, Carl H June
Replication-competent retrovirus/lentivirus (RCR/L) and insertional oncogenesis are potential safety risks with integrating viruses in gene-modified cell therapies. As such, the Food and Drug Administration guidances outline RCR/L-monitoring methods throughout the entire gene therapy treatment cycle. We present data for 17 vector lots, 375 manufactured T cell products, and 308 patients post-infusion across both HIV and oncology indications, showing no evidence of RCR/L. Given our data, a Poisson probability model estimates that a single patient, or a group of patients, would need to be followed for at least 52...
October 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29200184/structural-neuroimaging-and-neuropsychologic-signatures-of-vertically-acquired-hiv
#18
Robert Paul, Wasana Prasitsuebsai, Neda Jahanashad, Thanyawee Puthanakit, Paul Thompson, Linda Aurpibul, Rawiwan Hansudewechakul, Pope Kosalaraksa, Suparat Kanjanavanit, Chaiwat Ngampiyaskul, Wicharn Luesomboon, Sukalaya Lerdlum, Mantana Pothisri, Pannee Visrutaratna, Victor Valcour, Talia M Nir, Arvin Saremi, Stephen Kerr, Jintanat Ananworanich
BACKGROUND: Children with vertically acquired human immunodeficiency virus (HIV) exhibit persistent cognitive impairments, yet the corresponding neuroimaging signature of vertical infection remains unclear. METHODS: Fifty healthy control children and 51 vertically infected children were included in the study. The HIV-infected group consisted of survivors who had not received antiretroviral therapy (ART) at birth. The HIV-infected group averaged 11.4 (2.5) years of age, with a median CD4 count of 683 cells/mm...
December 1, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29187544/genetically-intact-but-functionally-impaired-hiv-1-env-glycoproteins-in-the-t-cell-reservoir
#19
Anne de Verneuil, Julie Migraine, Fabrizio Mammano, Jean-Michel Molina, Sébastien Gallien, Hugo Mouquet, Allan J Hance, François Clavel, Jacques Dutrieux
HIV-infected subjects under ART harbor a persistent viral reservoir in resting CD4+ T-cells, which accounts for the resurgence of HIV replication after ART interruption. A large majority of HIV reservoir genomes are genetically defective, but even among intact proviruses, few seem able to generate infectious virus. To understand this phenomenon, we have examined the function and expression of HIV envelope glycoproteins reactivated from the reservoir of 4 HIV-infected subjects under suppressive ART. We studied full-length genetically intact env sequences from both replicative viruses and cell-associated mRNAs...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29186062/viral-oncology-molecular-biology-and-pathogenesis
#20
REVIEW
Uyen Ngoc Mui, Christopher T Haley, Stephen K Tyring
Oncoviruses are implicated in approximately 12% of all human cancers. A large number of the world's population harbors at least one of these oncoviruses, but only a small proportion of these individuals go on to develop cancer. The interplay between host and viral factors is a complex process that works together to create a microenvironment conducive to oncogenesis. In this review, the molecular biology and oncogenic pathways of established human oncoviruses will be discussed. Currently, there are seven recognized human oncoviruses, which include Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), Human T-cell lymphotropic virus-1 (HTLV-1), Human Herpesvirus-8 (HHV-8), and Merkel Cell Polyomavirus (MCPyV)...
November 29, 2017: Journal of Clinical Medicine
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