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https://www.readbyqxmd.com/read/28922253/long-term-efficacy-safety-and-immunogenicity-of-biosimilar-infliximab-after-one-year-in-a-prospective-nationwide-cohort
#1
Lorant Gonczi, Krisztina B Gecse, Zsuzsanna Vegh, Zsuzsanna Kurti, Mariann Rutka, Klaudia Farkas, Petra A Golovics, Barbara D Lovasz, Janos Banai, Laszlo Bene, Bea Gasztonyi, Tunde Kristof, Laszlo Lakatos, Pal Miheller, Ferenc Nagy, Karoly Palatka, Maria Papp, Arpad Patai, Agnes Salamon, Tamas Szamosi, Zoltan Szepes, Gabor T Toth, Aron Vincze, Balazs Szalay, Tamas Molnar, Peter L Lakatos
BACKGROUND: It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort. METHODS: A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC)...
August 23, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#2
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28914348/immunogenicity-and-antimicrobial-effectiveness-of-pseudomonas-aeruginosa-specific-bacteriophage-in-a-human-lung-in-vitro-model
#3
Joseph R Shiley, Kristen K Comfort, Jayne B Robinson
The rise of antibiotic resistant bacteria is posing a serious threat to human health. For example, resistant strains of Pseudomonas aeruginosa have resulted in untreatable and potentially lethal infections in both cystic fibrosis and immunocompromised patients. Due to the growing need for alternative treatment options, bacteriophage, or phage, therapy is gaining considerable attention. While previous studies have demonstrated the effectiveness of phage in combating persistent bacterial infections, there is currently a lack of knowledge regarding the host immunological response following phage exposure...
September 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28906475/can-we-predict-the-efficacy-of-anti-tnf-%C3%AE-agents
#4
REVIEW
Loris Riccardo Lopetuso, Viviana Gerardi, Valerio Papa, Franco Scaldaferri, Gian Lodovico Rapaccini, Antonio Gasbarrini, Alfredo Papa
The use of biologic agents, particularly anti-tumor necrosis factor (TNF)-α, has revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Several data on the efficacy of these agents in inducing and maintaining clinical remission have been accumulated over the past two decades: their use avoid the need for steroids therapy, promote mucosal healing, reduce hospitalizations and surgeries and therefore dramatically improve the quality of life of IBD patients. However, primary non-response to these agents or loss of response over time mainly due to immunogenicity or treatment-related side-effects are a frequent concern in IBD patients...
September 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28884416/repeated-stress-exaggerates-lipopolysaccharide-induced-inflammatory-response-in-the-rat-spleen
#5
M Laukova, Peter Vargovic, I Rokytova, G Manz, R Kvetnansky
Spleen is an immune organ innervated with sympathetic nerves which together with adrenomedullary system control splenic immune functions. However, the mechanism by which prior stress exposure modulates the immune response induced by immunogenic challenge is not sufficiently clarified. Thus, the aim of this study was to investigate the effect of a single (2 h) and repeated (2 h daily for 7 days) immobilization stress (IMO) on the innate immune response in the spleen induced by lipopolysaccharide (LPS, 100 µg/kg)...
September 7, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28878289/persistence-within-dendritic-cells-marks-an-antifungal-evasion-and-dissemination-strategy-of-aspergillus-terreus
#6
Shih-Hung Hsieh, Oliver Kurzai, Matthias Brock
Aspergillus terreus is an airborne human fungal pathogen causing life-threatening invasive aspergillosis in immunocompromised patients. In contrast to Aspergillus fumigatus, A. terreus infections are associated with high dissemination rates and poor response to antifungal treatment. Here, we compared the interaction of conidia from both fungal species with MUTZ-3-derived dendritic cells (DCs). After phagocytosis, A. fumigatus conidia rapidly escaped from DCs, whereas A. terreus conidia remained persisting with long-term survival...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877927/protective-vaccine-efficacy-of-the-complete-form-of-ppe39-protein-from-mycobacterium-tuberculosis-beijing-k-strain-in-mice
#7
Ahreum Kim, Yun-Gyoung Hur, Sunwha Gu, Sang-Nae Cho
The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guérin, or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tb-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides...
September 6, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28851629/immunogenicity-of-virus-like-semliki-forest-virus-replicon-particles-expressing-indian-hiv-1c-gag-env-and-polrt-genes
#8
Seema P Ajbani, Shilpa M Velhal, Ravindra B Kadam, Vainav V Patel, Kenneth Lundstrom, Atmaram H Bandivdekar
Development of a vaccine targeting human immunodeficiency virus-1 subtype C (HIV-1C) is an important public health priority in regions with a high prevalence of the clade C virus. The present study demonstrates the immunogenicity of recombinant Semliki Forest virus (SFV)-based virus-like replicon particles (VRPs) expressing Indian HIV-1C env/gag/polRT genes. Immunization of mice with recombinant VRPs in a homologous prime-boost protocol, either individually or in combination, elicited significant antigen-specific IFN-γ T cell responses as detected by the ELISPOT assay...
August 26, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28819247/delta-inulin-based-adjuvants-promote-the-generation-of-polyfunctional-cd4-t-cell-responses-and-protection-against-mycobacterium-tuberculosis-infection
#9
Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J Britton, Nikolai Petrovsky, James A Triccas
There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816757/therapeutic-drug-monitoring-during-induction-of-anti-tumor-necrosis-factor-therapy-in-inflammatory-bowel-disease-defining-a-therapeutic-drug-window
#10
Konstantinos Papamichael, Niels Vande Casteele, Marc Ferrante, Ann Gils, Adam S Cheifetz
Anti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical benefit and are defined as having a primary nonresponse. Primary nonresponse to a biologic can be attributed to either pharmacokinetic or pharmacodynamic issues, such as those involved in secondary loss of response. Pharmacokinetic issues are linked to undetectable or subtherapeutic drug concentrations because of either an accelerated non-immune-mediated clearance or immunogenicity and the development of antidrug antibodies, whereas pharmacodynamic issues are likely related to "non-TNF driven" disease...
September 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28816748/therapeutic-drug-monitoring-during-induction-of-anti-tumor-necrosis-factor-therapy-in-inflammatory-bowel-disease-defining-a-therapeutic-drug-window
#11
Konstantinos Papamichael, Niels Vande Casteele, Marc Ferrante, Ann Gils, Adam S Cheifetz
Anti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical benefit and are defined as having a primary nonresponse. Primary nonresponse to a biologic can be attributed to either pharmacokinetic or pharmacodynamic issues, such as those involved in secondary loss of response. Pharmacokinetic issues are linked to undetectable or subtherapeutic drug concentrations because of either an accelerated non-immune-mediated clearance or immunogenicity and the development of antidrug antibodies, whereas pharmacodynamic issues are likely related to "non-TNF driven" disease...
August 14, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28803431/sb2-an-infliximab-biosimilar
#12
Yvette N Lamb, Lesley J Scott, Emma D Deeks
SB2 is a biosimilar of the reference anti-TNF-α antibody infliximab. In May 2015, it was approved in the EU for use in all indications for which reference infliximab is approved, including rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriatic arthritis and psoriasis. It is also approved in these indications in several other countries, including Korea, the USA and Australia. Characterization of SB2 in preclinical studies showed that it is similar to reference infliximab...
August 12, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28802400/mycobacterium-tuberculosis-myma-is-a-tlr2-agonist-that-activate-macrophages-and-a-th1-response
#13
Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma
Cell wall of Mycobacterium tuberculosis (M.tb) is a major source of immunogenic proteins that can be tested as vaccine candidates. MymA (Rv3083), a 55 kDa M.tb flavin containing monooxygenase, is involved in modification of mycolic acids during acidic shock following M.tb internalization in macrophage. In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) engagement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28800777/bortezomib-treatment-induces-a-higher-mortality-rate-in-lupus-model-mice-with-a-higher-disease-activity
#14
Tomoko Ikeda, Hiroshi Fujii, Masato Nose, Yukiko Kamogawa, Tsuyoshi Shirai, Yuko Shirota, Tomonori Ishii, Hideo Harigae
BACKGROUND: Bortezomib (Bz) is a proteasome inhibitor that directly targets antibody-producing plasma cells. We recently reported the first randomized control trial that evaluated the effects of Bz in patients with systemic lupus erythematosus (SLE). In that study, we demonstrated that Bz treatment is associated with many adverse reactions in patients with refractory disease. In the present study, we examine the therapeutic and toxic effects of Bz on MRL/MpJ-lpr/lpr (MRL/lpr) mice with severe disease activity...
August 11, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28799018/an-immunogenic-peptide-t2-induces-interstitial-cystitis-painful-bladder-syndrome-an-autoimmune-mouse-model-for-interstitial-cystitis-painful-bladder-syndrome
#15
Li Zhang, Awais Ullah Ihsan, Yanfang Cao, Farhan Ullah Khan, Yijie Cheng, Lei Han, Xiaohui Zhou
The exact pathophysiology of interstitial cystitis/painful bladder syndrome is unknown; however, autoimmunity is a valid theory. We developed an autoimmune chronic cystitis model by administration of the medium dose of immunogenic peptide T2. Sixty female C57BL/6 mice were divided into six groups. The control group was not treated with any reagent. CFA group was injected with CFA + normal saline, homogenate group with bladder homogenate + CFA, low-dose group with low dose of T2 peptide + CFA, medium dose group with the medium dose of T2 peptide + CFA, and high-dose group with the high dose of T2 peptide + CFA...
August 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28772079/biological-anti-tnf-drugs-immunogenicity-underlying-treatment-failure-and-adverse-events
#16
REVIEW
Mônica Simon Prado, Klaus Bendtzen, Luis Eduardo Coelho Andrade
Genetically engineered monoclonal antibodies and fusion proteins directed against cytokines or their receptors represent a breakthrough in the treatment of various chronic immune-inflammatory diseases. Areas covered: Studies show high remission rates in several diseases, but clinical practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28769101/allostimulatory-capacity-of-conditionally-immortalized-proximal-tubule-cell-lines-for-bioartificial-kidney-application
#17
Milos Mihajlovic, Lambertus P van den Heuvel, Joost G Hoenderop, Jitske Jansen, Martijn J Wilmer, Annemarie J F Westheim, Wil A Allebes, Dimitrios Stamatialis, Luuk B Hilbrands, Rosalinde Masereeuw
Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the alloimmunization and related safety aspects of readily available conditionally immortalized human proximal tubule epithelial cell (ciPTEC) lines to be used in BAK. Two ciPTEC lines, originally derived from urine and kidney tissue, were characterized for the expression and secretion of relevant molecules involved in alloimmunization and inflammatory responses, such as HLA class-I, HLA-DR, CD40, CD80, CD86, as wells as soluble HLA class I and proinflammatory cytokines (IL-6, IL-8 and TNF-α)...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767693/dendritic-cells-that-phagocytose-apoptotic-macrophages-loaded-with-mycobacterial-antigens-activate-cd8-t-cells-via-cross-presentation
#18
Patricia Espinosa-Cueto, Alejandro Magallanes-Puebla, Carlos Castellanos, Raul Mancilla
While homeostatic apoptosis is immunologically silent, macrophage apoptosis during Mycobacterium tuberculosis infection can potentially induce an immune response against the mycobacteria. To examine the role of dendritic cells in this response, macrophage apoptosis was induced by incubating the macrophage with cell wall extracts of mycobacteria expressing LpqH. The apoptogenic proteins of the cell wall extracts were engulfed by the macrophage and then were translocated from the cytosol to the nuclei of the dying cells...
2017: PloS One
https://www.readbyqxmd.com/read/28767653/in-silico-analysis-to-identify-vaccine-candidates-common-to-multiple-serotypes-of-shigella-and-evaluation-of-their-immunogenicity
#19
Sapna Pahil, Neelam Taneja, Hifzur Rahman Ansari, G P S Raghava
Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp...
2017: PloS One
https://www.readbyqxmd.com/read/28746871/the-histone-methyltransferase-ezh2-controls-mechanisms-of-adaptive-resistance-to-tumor-immunotherapy
#20
Daniel Zingg, Natalia Arenas-Ramirez, Dilara Sahin, Rodney A Rosalia, Ana T Antunes, Jessica Haeusel, Lukas Sommer, Onur Boyman
Immunotherapy and particularly immune checkpoint inhibitors have resulted in remarkable clinical responses in patients with immunogenic tumors, although most cancers develop resistance to immunotherapy. The molecular mechanisms of tumor resistance to immunotherapy remain poorly understood. We now show that induction of the histone methyltransferase Ezh2 controls several tumor cell-intrinsic and extrinsic resistance mechanisms. Notably, T cell infiltration selectively correlated with high EZH2-PRC2 complex activity in human skin cutaneous melanoma...
July 25, 2017: Cell Reports
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