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https://www.readbyqxmd.com/read/29156047/immunopathogenesis-of-hepatitis-b-virus
#1
Tai-Chung Tseng, Li-Rung Huang
Chronic hepatitis B virus (HBV) infection is a global public health issue. There are >250 million people chronically infected with HBV, and these chronic carriers are at high risk of developing end-stage liver diseases and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) usually acquire the virus perinatally, while most patients infected during adulthood develop acute hepatitis B (AHB), which usually results in viral clearance. HBV infection is noncytopathic, and liver injury is mostly contributed by host immune responses...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29155454/harnessing-the-power-of-regulatory-t-cells-to-control-autoimmune-diabetes-overview-and-perspective
#2
REVIEW
Hua Yu, Ricardo Paiva, Richard A Flavell
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T cells (Teff) and regulatory T cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity...
November 20, 2017: Immunology
https://www.readbyqxmd.com/read/29154771/in-vitro-blockade-of-the-cd4-receptor-co-signal-in-antigen-specific-t-cell-stimulation-cultures-induces-the-outgrowth-of-potent-cd4-independent-t-cell-effectors
#3
Sarah Vatter, Maximilian Schmid, Claudia Gebhard, Carina Mirbeth, Sebastian Klobuch, Michael Rehli, Wolfgang Herr, Simone Thomas
T-cell receptor (TCR) redirected T cells are promising tools for adoptive cancer immunotherapy. Since not only CD8 but also CD4 T cells are key players for efficient antitumor responses, the targeted redirection of both subsets with the same antigen-specific TCR comes more and more into focus. Although rapidly evolving technologies enable the reliable genetic re-programming of T cells, the limited availability of TCRs that induce T-cell activation in both T-cell subsets without CD4/CD8 co-receptor contribution hampers the broad application of this approach...
November 14, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29153071/-mycoviruses-and-importance-in-mycology
#4
Sema Aşkın Keçeli
Opportunistic fungal infections like invasive candidiasis and aspergillozis have high mortality rate particularly in immunosupressive patients. The rate of therapy success with antifungal agents is usually low. Although immunotherapy methods have been developed to increase the host response against antifungals, there has been a need for new antifungal therapeutic agents in the treatment of invasive aspergillozis and other opportunistic fungal infections. Mycoviruses are the viruses that specifically infect fungi...
October 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/29152306/evaluation-of-two-high-throughput-proteomic-technologies-for-plasma-biomarker-discovery-in-immunotherapy-treated-melanoma-patients
#5
Su Yin Lim, Jenny H Lee, Sarah J Welsh, Seong Beom Ahn, Edmond Breen, Alamgir Khan, Matteo S Carlino, Alexander M Menzies, Richard F Kefford, Richard A Scolyer, Georgina V Long, Helen Rizos
Background: Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment however, and some patients will present with significant toxicities. Hence, the identification of biomarkers is critical for the selection and management of patients receiving treatment. Biomarker discovery often involves proteomic techniques that simultaneously profile multiple proteins but few studies have compared these platforms...
2017: Biomarker Research
https://www.readbyqxmd.com/read/29152058/effective-control-of-acute-myeloid-leukaemia-and-acute-lymphoblastic-leukaemia-progression-by-telomerase-specific-adoptive-t-cell-therapy
#6
Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T Scupoli, Michael I Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte, Stefano Ugel
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151956/strategies-for-bispecific-single-chain-antibody-in-cancer-immunotherapy
#7
REVIEW
Shu-Juan Zhou, Jia Wei, Shu Su, Fang-Jun Chen, Yu-Dong Qiu, Bao-Rui Liu
Genetic engineering has resulted in more than 50 recombinant bispecific antibody formats over the past two decades. Bispecific scFv antibodies represent a successful and promising immunotherapy platform that retargets cytotoxic T cells to tumor cells, with one scFv directed to tumor-associated antigens and the other to T cells. Based on this antibody construct, strategies for both specific tumor targeting and T cell activation are reviewed here. Three distinct types of tumor antigens are considered to optimize specificity and safety in bispecific scFv based treatment: cancer-testis antigens, neo-antigens and virus-associated antigens...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29150857/a-randomized-double-blind-placebo-controlled-dose-finding-trial-with-lolium-perenne-peptide-immunotherapy
#8
Ralph Mösges, Elena M Kasche, Esther Raskopf, Jaswinder Singh, Lea Sohlich, Anatoli Astvatsatourov, Kija Shah-Hosseini, Sabine Pirotton, Ludo Haazen, Stephen R Durham, Thierry Legon, Gregor Zadoyan, Mohamed H Shamji
BACKGROUND: A novel subcutaneous allergen immunotherapy formulation (gpASIT+(™) ) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity, and safety. METHODS: This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170, or 370 μg LPP...
November 18, 2017: Allergy
https://www.readbyqxmd.com/read/29150848/allergen-manufacturing-and-quality-aspects-for-allergen-immunotherapy-in-europe-and-the-united-states-an-analysis-from-the-eaaci-ait-guidelines-project
#9
REVIEW
A Bonertz, G Roberts, J E Slater, J Bridgewater, R L Rabin, M Hoefnagel, M Timon, C Pini, O Pfaar, A Sheikh, D Ryan, C Akdis, J Goldstein, L K Poulsen, R van Ree, C Rhyner, D Barber, O Palomares, R Pawankar, D Hamerlijnk, L Klimek, I Agache, E Angier, T Casale, M Fernandez-Rivas, S Halken, M Jutel, S Lau, G Pajno, G Sturm, E M Varga, R Gerth van Wijk, S Bonini, A Muraro, S Vieths
Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States...
November 17, 2017: Allergy
https://www.readbyqxmd.com/read/29150846/cancer-stem-cells-as-targets-for-immunotherapy
#10
REVIEW
Amy S Codd, Takayuki Kanaseki, Toshihiko Torigo, Zsuzsanna Tabi
Current cancer therapies target the bulk of the tumour, while a population of highly resistant tumour cells may be able to repopulate the tumour and metastasise to new sites. Cancer cells with such stem cell-like characteristics can be identified based on their phenotypic and/or functional features which may open up ways for their targeted elimination. In this review we discuss potential off-target effects of inhibiting cancer stem-cell self-renewal pathways on immune cells, and summarise some recent immunological studies specifically targeting cancer stem cells based on their unique antigen expression...
November 18, 2017: Immunology
https://www.readbyqxmd.com/read/29150718/re-educating-immunity-in-respiratory-allergies-the-potential-for-hematopoietic-stem-cell-mediated-gene-therapy
#11
REVIEW
Jeremy F Brooks, Janet M Davies, James W Wells, Raymond J Steptoe
Respiratory allergies represent a significant disease burden worldwide affecting up to 300 million people globally. Medication and avoidance of known triggers do not address the underlying pathology. Traditional immunotherapies for allergy aim to reinstate immune homeostasis but require years of treatment and have poor long-term efficacy. Novel approaches, such as gene-engineered hematopoietic stem cell transplantation, induce profound antigen-specific tolerance in autoimmunity. Recent evidence shows this approach may also have therapeutic utility for allergy...
November 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29150702/high-pdl1-mrna-expression-predicts-better-survival-of-stage-pt1-non-muscle-invasive-bladder-cancer-nmibc-patients
#12
Johannes Breyer, Ralph M Wirtz, Wolfgang Otto, Philipp Erben, Thomas S Worst, Robert Stoehr, Markus Eckstein, Stefan Denzinger, Maximilian Burger, Arndt Hartmann
INTRODUCTION AND OBJECTIVES: Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification. MATERIALS AND METHODS: We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder...
November 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29150430/interferon-%C3%A1%C2%B5-2-signaling-in-melanocytes-and-melanoma-cells-regulates-expression-of-ctla-4
#13
Xuan Mo, Hanghang Zhang, Sarah Preston, Kayla Martin, Bo Zhou, Nish Vadalia, Ana M Gamero, Jonathan Soboloff, Italo Tempera, M Raza Zaidi
CTLA-4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti-CTLA-4 immunotherapy is highly effective at reactivating T cell responses against melanoma, which is postulated to be due to targeting CTLA-4 on T cells. Here we report that CTLA-4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-gamma (IFNG) signaling activated the expression of the human CTLA-4 gene in a melanocyte and melanoma cell-specific manner...
November 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29147793/pharmacophoric-characteristics-of-dengue-virus-ns2b-ns3pro-inhibitors-a-systematic-review-of-the-most-promising-compounds
#14
REVIEW
Camyla Alves Leonel, William Gustavo Lima, Michelli Dos Santos, Ariane Coelho Ferraz, Alex Gutterres Taranto, José Carlos de Magalhães, Luciana Lara Dos Santos, Jaqueline Maria Siqueira Ferreira
Dengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease due to the lack of specific immunotherapies and antiviral drugs. That said, the DENV NS2B/NS3pro protease complex is essential in both the viral multiplication cycle and in disease pathogenesis, and is considered a promising target for new antiviral therapies. Here, we performed a systematic review to evaluate the pharmacophoric characteristics of promising compounds against NS2B/NS3pro reported in the past 10 years...
November 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29147629/trial-watch-immune-checkpoint-blockers-for-cancer-therapy
#15
REVIEW
Claire Vanpouille-Box, Claire Lhuillier, Lucillia Bezu, Fernando Aranda, Takahiro Yamazaki, Oliver Kepp, Jitka Fucikova, Radek Spisek, Sandra Demaria, Silvia C Formenti, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Immune checkpoint blockers (ICBs) are literally revolutionizing the clinical management of an ever more diversified panel of oncological indications. Although considerable attention persists around the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death 1 (PDCD1, best known as PD-1) signaling, several other co-inhibitory T-cell receptors are being evaluated as potential targets for the development of novel ICBs. Moreover, substantial efforts are being devoted to the identification of biomarkers that reliably predict the likelihood of each patient to obtain clinical benefits from ICBs in the absence of severe toxicity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147628/trial-watch-adoptively-transferred-cells-for-anticancer-immunotherapy
#16
REVIEW
Carole Fournier, François Martin, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi, Lionel Apetoh
Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147626/functional-t-cells-targeting-tumor-associated-antigens-are-predictive-for-recurrence-free-survival-of-patients-with-radically-operated-non-small-cell-lung-cancer
#17
Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove
In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#18
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147610/host-immune-response-index-in-gastric-cancer-identified-by-comprehensive-analyses-of-tumor-immunity
#19
Charny Park, Junhun Cho, Jeeyun Lee, So Young Kang, Ji Yeong An, Min Gew Choi, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Won Ki Kang, Insuk Sohn, Sin Ho Jung, Myung-Soo Kang, Kyoung-Mee Kim
Tumor infiltrating lymphocytes (TIL) in Epstein-Barr virus (EBV)-associated/microsatellite-unstable (MSI) gastric carcinomas (GC) constitute immune-active principal cellular components of tumor microenvironment and contribute to better prognosis. With the remarkable success of cancer immunotherapies, there is an urgent need for a comprehensive understanding of tumor-immune interactions in patients with GC in the context of host immune response. To identify GC subtype-specific immune response gene set, we tested differentially expressed genes for MSI and EBV+ GC subtypes in randomly selected test set (n = 278) in merged ACRG-SMC microarray and TCGA RNA sequencing data set...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146881/beta-adrenergic-signaling-impairs-anti-tumor-cd8-t-cell-responses-to-b-cell-lymphoma-immunotherapy
#20
Michael D Nissen, Erica K Sloan, Stephen R Mattarollo
Beta-adrenergic receptor (betaAR) signaling regulates many physiological processes, including immune system responses. There is growing evidence also for betaAR-induced modulation of cancer growth and metastasis. In the Eu-myc mouse model of B-cell lymphoma, we investigated the effects of chronically elevated betaAR signaling on lymphoma progression and anti-tumor immunity, as well as the impact on cancer immunotherapy. Chronic treatment with the non-selective beta-agonist isoprenaline promoted lymphoma development in a manner dependent on signaling within the hematopoietic compartment...
November 16, 2017: Cancer Immunology Research
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