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https://www.readbyqxmd.com/read/28803431/sb2-an-infliximab-biosimilar
#1
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
#2
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
#3
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
#4
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
#5
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...
August 3, 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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28744638/counts-of-msc-in-the-bone-marrow-of-young-and-old-cba-mice-after-a-single-exposure-to-osteogenic-stimuli-curettage-bmp-2-injection-or-antigens-s-typhimurium-antigenic-complex-and-in-heterotopic-bone-marrow-transplants
#10
Yu F Gorskaya, A Sh Dzharullaeva, D S Onsina, V G Nesterenko
The efficiency of cloning and the content of multipotent stromal cells (MSC) in the femoral bone marrow of intact CBA mice was 1.5 times less in old mice (24-36 months) than in young ones (2-3 months). The concentration of osteogenic MSC was higher in old vs. young mice (42±3 vs. 22±2%, respectively). Changes in the total counts of MSC and concentrations of osteogenic MSC in response to osteogenic (curettage, BMP-2) and immunogenic stimuli (S. typhimurium antigenic complex) were similar in young and old mice in comparison with intact controls of respective age...
July 25, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28739115/a-recombinant-protein-of-salmonella-typhi-induces-humoral-and-cell-mediated-immune-responses-including-memory-responses
#11
Sayan Das, Rimi Chowdhury, Shubhamoy Ghosh, Santasabuj Das
Gram negative enteric bacteria, Salmonella enterica serovar Typhi (S. Typhi), the etiological agent of typhoid fever is a major public health problem in developing countries. While a permanent solution to the problem would require improved sanitation, food and water hygiene, controlling the infection by vaccination is urgently required due to the emergence of multidrug resistant strains in multiple countries. The currently licensed vaccines are moderately efficacious with limited applicability, and no recommended vaccines exist for younger children...
July 21, 2017: Vaccine
https://www.readbyqxmd.com/read/28737923/cosilencing-intestinal-transglutaminase-2-and-interleukin-15-using-gelatin-based-nanoparticles-in-an-in-vitro-model-of-celiac-disease
#12
Husain Attarwala, Valerie Clausen, Prasoon Chaturvedi, Mansoor M Amiji
In this study, we have developed a type B gelatin nanoparticle based siRNA delivery system for silencing of intestinal transglutaminase-2 (TG2) and interleukin-15 (IL-15) genes in cultured human intestinal epithelial cells (Caco-2) and murine alveolar macrophage cells (J774A.1). Small interfering RNA (siRNA) targeting the TG2 or IL-15 gene was encapsulated within gelatin nanoparticles using ethanol-water solvent displacement method. Size, charge, and morphology of gelatin nanoparticles were evaluated using a Zetasizer instrument and transmission electron microscopy...
August 10, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28728855/tissue-plasminogen-activator-tpa-signal-sequence-enhances-immunogenicity-of-mva-based-vaccine-against-tuberculosis
#13
Yiming Kou, Yongqing Xu, Zhilei Zhao, Jie Liu, Yang Wu, Qingrui You, Linli Wang, Feng Gao, Linjun Cai, Chunlai Jiang
Tuberculosis (TB) remains a serious health problem worldwide, and the only available vaccine, bacillus Calmette-Guérin (BCG), has shown highly variable efficacy in adults against TB. New vaccines are urgently needed, and the modified vaccinia virus Ankara (MVA)-based vaccine has emerged as one of the most promising candidates based on many preclinical and early clinical studies over the past few years. However, the maximum tolerable dose and strength of induced immune responses have limited the protective effect of MVA-based prophylactic vaccines...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28719652/long-term-follow-up-of-human-t-cell-responses-to-conserved-hiv-1-regions-elicited-by-dna-simian-adenovirus-mva-vaccine-regimens
#14
Nathifa Moyo, Nicola J Borthwick, Edmund G Wee, Silvia Capucci, Alison Crook, Lucy Dorrell, Tomáš Hanke
BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8+ T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8+ T cells capable of in vitro HIV-1 inhibition...
2017: PloS One
https://www.readbyqxmd.com/read/28719541/systematic-review-and-meta-analysis-adalimumab-monotherapy-versus-combination-therapy-with-immunomodulators-for-induction-and-maintenance-of-remission-and-response-in-patients-with-crohn-s-disease
#15
Jean M Chalhoub, Hussein H Rimmani, Vivek V Gumaste, Ala I Sharara
BACKGROUND: It is unclear whether the combination of adalimumab (ADA) and immunomodulators is superior to ADA monotherapy in patients with Crohn's disease. METHODS: PubMed, Medline, Embase, Web of Science, and other databases were searched. Randomized controlled trials, open-label, prospective cohort, and retrospective studies, and pooled analyses were included. Primary outcomes were induction (≤12 wk) and maintenance (up to 56 wk) of remission and response. Secondary outcomes were severe adverse events, opportunistic infections, and development of antibodies to adalimumab...
August 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28700520/current-practice-for-therapeutic-drug-monitoring-of-biopharmaceuticals-in-rheumatoid-arthritis
#16
Frédéric Medina, Chamaida Plasencia, Philippe Goupille, David Ternant, Alejandro Balsa, Denis Mulleman
The treatment of rheumatoid arthritis (RA) has largely improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF) inhibitors, are effective, but some patients may show poor response, sometimes because of the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose depending on the clinical response. Besides the current clinical-based practice, a tailored strategy based on drug monitoring has emerged as a way to improve the use of these drugs...
August 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28697172/immunogenic-chemotherapy-sensitizes-renal-cancer-to-immune-checkpoint-blockade-therapy-in-preclinical-models
#17
Shujin Cui
BACKGROUND Renal cell carcinoma (RCC) is among the most common malignant cancers of males worldwide. For advanced RCC patients, there still is no effective therapy. Immune checkpoint blockade therapies have shown benefits for many cancers, but previous clinical trials of immune checkpoint blockade therapies in RCC patients achieved only modest results. MATERIAL AND METHODS We explored the effects of combining chemotherapy with immune checkpoint blockade therapy in RCC xenograft mouse models. We also studied the potential mechanisms by which chemotherapy might enhance the efficacy of immune checkpoint blockade therapy, both in vitro and in vivo...
July 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28657381/safety-profile-of-biological-therapies-for-treating-rheumatoid-arthritis
#18
Juan D Cañete, Mª Victoria Hernández, Raimon Sanmartí
Biological agents such as tumor necrosis factor inhibitors (TNFi), abatacept, rituximab and tocilizumab have proven efficacy in RA. However, these agents are also associated with adverse events so further data is essential to detect them at the earliest stage possible. Areas covered: Herein, the authors review the safety profile of biological therapy, including TNFi and non-TNF agents including abatacept (ABA), rituximab (RTX) and tocilizumab (TCZ). The authors analyze both published articles and congress communications including clinical trials, meta-analyses, observational studies, data from registries and spontaneous clinical reports...
July 17, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28648866/cytokines-in-immunogenic-cell-death-applications-for-cancer-immunotherapy
#19
REVIEW
Anne Showalter, Arati Limaye, Jeremiah L Oyer, Robert Igarashi, Christina Kittipatarin, Alicja J Copik, Annette R Khaled
Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions...
September 2017: Cytokine
https://www.readbyqxmd.com/read/28647488/autoreactivity-to-malondialdehyde-modifications-in-rheumatoid-arthritis-is-linked-to-disease-activity-and-synovial-pathogenesis
#20
Caroline Grönwall, Khaled Amara, Uta Hardt, Akilan Krishnamurthy, Johanna Steen, Marianne Engström, Meng Sun, A Jimmy Ytterberg, Roman A Zubarev, Dagmar Scheel-Toellner, Jeffrey D Greenberg, Lars Klareskog, Anca I Catrina, Vivianne Malmström, Gregg J Silverman
Oxidation-associated malondialdehyde (MDA) modification of proteins can generate immunogenic neo-epitopes that are recognized by autoantibodies. In health, IgM antibodies to MDA-adducts are part of the natural antibody pool, while elevated levels of IgG anti-MDA antibodies are associated with inflammatory and autoimmune conditions. Yet, in human autoimmune disease IgG anti-MDA responses have not been well characterized and their potential contribution to disease pathogenesis is not known. Here, we investigate MDA-modifications and anti-MDA-modified protein autoreactivity in rheumatoid arthritis (RA)...
June 21, 2017: Journal of Autoimmunity
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