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immunogenicity TNF

Shimpei Shirai, Megumi Hara, Yasuhisa Sakata, Nanae Tsuruoka, Koji Yamamoto, Ryo Shimoda, Yasuyuki Gomi, Hironori Yoshii, Kazuma Fujimoto, Ryuichi Iwakiri
Background and Aims: No reports have described the immunogenicity and boosting effect of the quadrivalent inactivated influenza vaccine (QIV) in adults with inflammatory bowel disease. Methods: Adults with Crohn's disease or ulcerative colitis were randomly assigned to a single vaccination group or booster group, and a QIV was administered subcutaneously. Serum samples were collected before vaccination, 4 weeks after vaccination, and after the influenza season in the single vaccination group...
March 9, 2018: Inflammatory Bowel Diseases
Franklin R Toapanta, Paula J Bernal, Karen L Kotloff, Myron M Levine, Marcelo B Sztein
BACKGROUND: Shigellosis persists as a public health problem worldwide causing ~ 165,000 deaths every year, of which ~ 55,000 are in children less than 5 years of age. No vaccine against shigellosis is currently licensed. The live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S (S. flexneri 2a; ΔguaBA, Δset, Δsen) demonstrated to be safe and immunogenic in phase 1 and 2 clinical trials. Earlier reports focused on humoral immunity. However, Shigella is an intracellular pathogen and therefore, T cell mediated immunity (T-CMI) is also expected to play an important role...
March 13, 2018: Journal of Translational Medicine
Fang-Yuan Gong, Zheng Gong, Cui-Cui Duo, Jun Wang, Chao Hong, Xiao-Ming Gao
Calreticulin (CRT), a luminal resident calcium-binding glycoprotein of the cell, is a tumor-associated antigen involved in tumorigenesis and also an autoantigen targeted by autoantibodies found in patients with various autoimmune diseases. We have previously shown that prokaryotically expressed recombinant murine CRT (rCRT) exhibits strong stimulatory activities against monocytes/macrophages in vitro and potent immunogenicity in vivo, which is partially attributable to self-oligomerization of soluble rCRT. However, even in oligomerized form native CRT (nCRT) isolated from mouse liver is much less active than rCRT, arguing against the possibility that self-oligomerization alone would license potent pro-inflammatory properties to nCRT...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sizheng Zhao, Eduardo Mysler, Robert J Moots
Etanercept was the first specific anticytokine therapy approved for the treatment of rheumatoid arthritis (RA). Its clinical efficacy and safety has been demonstrated by several clinical trials in early as well as established disease. Etanercept, along with other TNF inhibitors, have revolutionized management of RA and dramatically improved disease activity, function, quality of life and mortality for these patients. It is structurally distinct from other TNF inhibitors and thus has desirable profiles for immunogenicity, drug survival and infection rate...
February 27, 2018: Immunotherapy
Steven Bots, Krisztina Gecse, Murray Barclay, Geert D'Haens
Whether to use biologic treatment for inflammatory bowel disease as monotherapy or in combination with immunosuppressives has been a matter of debate in the last 2 decades. Combination therapy was not superior in any of the registration trials for Crohn's disease and ulcerative colitis for TNF antagonists, vedolizumab, or ustekinumab. It needs to be mentioned, though, that none of these trials were powered to detect such differences, and that many patients entered the trial after having failed conventional immunosuppressives...
February 15, 2018: Inflammatory Bowel Diseases
Dzul-Rosado Karla, Balam-Romero Javier, Valencia-Pacheco Guillermo, Lugo-Caballero Cesar, Arias-Leon Juan Jose, Peniche-Lara Gaspar, Zavala-Castro Jorge
Background & objectives: The nature of the rickettsial antigens and the immune response generated by them, have been the subject of exhaustive research so that a suitable vaccine can be developed. Till date evaluations of Rickettsia rickettsii antigens that induce both humoral and cellular responses in animal models have only shown partial protection and short-term immunological memory. This study was aimed to evaluate the immune response induced by DNA plasmids generated from the OmpA and OmpB genes of R...
October 2017: Journal of Vector Borne Diseases
Anna Buermann, Stoyan Petkov, Björn Petersen, Rabea Hein, Andrea Lucas-Hahn, Wiebke Baars, Antje Brinkmann, Heiner Niemann, Reinhard Schwinzer
BACKGROUND: The programmed cell death-1 (PD-1, CD279)/PD-Ligand1 (PD-L1, CD274) receptor system is crucial for controlling the balance between immune activation and induction of tolerance via generation of inhibitory signals. Expression of PD-L1 is associated with reduced immunogenicity and renders cells and tissues to an immune-privileged/tolerogenic state. METHODS: To apply this concept for clinical xenotransplantation, we generated human (h)PD-L1 transgenic pigs and characterized expression and biological function of the transgene at the cellular level...
February 15, 2018: Xenotransplantation
Curtis J Perry, Andrés R Muñoz-Rojas, Katrina M Meeth, Laura N Kellman, Robert A Amezquita, Durga Thakral, Victor Y Du, Jake Xiao Wang, William Damsky, Alexandra L Kuhlmann, Joel W Sher, Marcus Bosenberg, Kathryn Miller-Jensen, Susan M Kaech
Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state...
February 7, 2018: Journal of Experimental Medicine
Mathilde Bahuaud, Constance Beaudouin-Bazire, Marine Husson, Anna Molto, Odile Launay, Frédéric Batteux, Maxime Dougados
OBJECTIVES: Patients with rheumatoid arthritis (RA) are at an increased risk of Pneumococcal infections. Immunogenicity and persistence of a prime-boost revaccination strategy using 13-valent/23-valent anti-pneumococcal vaccines was evaluated in patients with RA treated by Methotrexate (MTX) and anti-TNF. METHOD: Twenty-four patients with RA received one dose of PCV13 (Prevenar13ࣨ; Pfizer) followed two months later by one dose of PPV23 (Pneumovax®, Merck). Concentrations of IgG specific for 7 serotypes common to both vaccines and 3 uncommon serotypes, included only in the PPV23 were measured by ELISA and Opsonophagocytic Assay (OPA) at baseline and after 4, 12 and 24 months post-vaccine...
February 12, 2018: Human Vaccines & Immunotherapeutics
B Gorovits, D J Baltrukonis, I Bhattacharya, M A Birchler, D Finco, D Sikkema, M S Vincent, S Lula, L Marshall, T P Hickling
OBJECTIVE: To examine the assay formats used to detect anti-drug antibodies (ADA) in clinical studies of the anti-TNF monoclonal antibodies adalimumab and infliximab in chronic inflammatory disease and their potential impact on pharmacokinetic and clinical outcomes. METHODS: Using findings of a recent systematic literature review of the immunogenicity of 11 biologic/biosimilar agents, we conducted an ancillary qualitative review of a subset of randomized controlled trials and observational studies of the monoclonal antibodies against anti-tumor necrosis factor adalimumab and infliximab...
February 12, 2018: Clinical and Experimental Immunology
A Barré, J-F Colombel, R Ungaro
BACKGROUND: Increased knowledge of pathways involved in the pathogenesis of IBD has led to the development of new treatment options for Crohn's disease (CD) and ulcerative colitis (UC). Two new biological agents have been recently approved for IBD: vedolizumab and ustekinumab. They have different therapeutic targets (α4 β7 integrin for vedolizumab and interleukin-12/23 pathways for ustekinumab) than the primary biological class, anti-tumour necrosis factor alpha (anti-TNF) agents. As the armamentarium for IBD increases in coming years, it will become important to understand factors associated with response in order to best position and personalise therapy...
February 12, 2018: Alimentary Pharmacology & Therapeutics
Chunhui Wu, Lianhui Wang, Yuan Tian, Xiaotian Guan, Qiuyue Liu, Shun Li, Xiang Qin, Hong Yang, Yi Yao Liu
Nanomedicine-based combination therapy has sparked a growing interest in clinical disease treatment and pharmaceutical industry. In this report, a mitochondria-targeted and near-infrared (NIR) light activable multitasking nanographene (i. e. GT/IR820/DP-CpG) had been engineered to in-situ trigger highly efficient 'triple-punch' strategy of cancer photodynamic therapy, photothermal therapy and immunotherapy. Modification of triphenylphosphonium on graphene made the vehicle specifically guide the NIR dye IR820 home to mitochondria followed by lysosomes escape in a time-dependent manner...
February 5, 2018: ACS Applied Materials & Interfaces
Anje Cauwels, Sandra Van Lint, Geneviève Garcin, Jennyfer Bultinck, Franciane Paul, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Lode De Cauwer, Elke Rogge, Annick Verhee, Gilles Uzé, Jan Tavernier
Despite approval for the treatment of various malignancies, clinical application of cytokines such as type I interferon (IFN) is severely impeded by their systemic toxicity. AcTakines (Activity-on-Target cytokines) are optimized immunocytokines that, when injected in mice, only reveal their activity upon cell-specific impact. We here show that type I IFN-derived AcTaferon targeted to the tumor displays strong antitumor activity without any associated toxicity, in contrast with wild type IFN. Treatment with CD20-targeted AcTaferon of CD20+ lymphoma tumors or melanoma tumors engineered to be CD20+, drastically reduced tumor growth...
2018: Oncoimmunology
Ruchi Rastogi, Arbind Kumar, Jagdeep Kaur, Varinder Saini, Jasbinder Kaur, Archana Bhatnagar
The genome sequence of Mycobacterium tuberculosis revealed the presence of several hydrolases involved in lipid metabolism including the members of Lip gene family. Rv0646c (LipG) is one of them. It is annotated as putative esterase/lipase because of the presence of consensus sequence 'GXSXG.' The gene was cloned, expressed, and purified in E. coli. It showed 22 U/mg specific activity with pNP-butyrate as a preferred substrate. However, it actively worked on substrates with short chain. The enzyme was optimally active at 50 °C/pH 8...
January 31, 2018: Molecular and Cellular Biochemistry
Juliette Sheridan, Carol Ann Coe, Peter Doran, Laurence Egan, Garret Cullen, David Kevans, Jan Leyden, Marie Galligan, Aoibhlinn O'Toole, Jane McCarthy, Glen Doherty
Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), often leading to an impaired quality of life in affected patients. Current treatment modalities include antitumour necrosis factor (anti-TNF) monoclonal antibodies (mABs) including infliximab, adalimumab and golimumab (GLM). Several recent retrospective and prospective studies have demonstrated that fixed dosing schedules of anti-TNF agents often fails to consistently achieve adequate circulating therapeutic drug levels (DL) with consequent risk of immunogenicity treatment failure and potential risk of hospitalisation and colectomy in patients with UC...
2018: BMJ Open Gastroenterology
Alejandro Balsa, Raimon Sanmarti, José Rosas, Victor Martin, Ana Cabez, Susana Gómez, María Montoro
Objectives: The aims were to evaluate the prevalence of anti-drug antibodies (ADA) in patients with RA or SpA experiencing secondary failure to anti-TNF therapy and to correlate ADA presence with anti-TNF concentration and clinical response. Methods: This was a cross-sectional, observational study of patients with active RA or SpA experiencing secondary failure to etanercept (ETN), infliximab (INF) or adalimumab (ADL). Concomitant non-biologic DMARDs were permitted...
January 19, 2018: Rheumatology
Perry K Pratt, Nunes David, Horst C Weber, Frédéric F Little, Themistoklis Kourkoumpetis, Gregory J Patts, Janice Weinberg, Francis A Farraye
Background: Studies have demonstrated an association between anti-TNF/immunomodulator agents used in inflammatory bowel disease (IBD) and impaired hepatitis B virus (HBV) vaccine immunogenicity, but little data exist on whether specific medication types affect protective HBsAb titers. Our aim was to analyze this association. Methods: This is a retrospective cohort study. Inclusion criteria: age ≥18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), previous HBV vaccination series and/or ≥1 positive HBsAb, and record of IBD therapy in 6 months before titer level...
January 18, 2018: Inflammatory Bowel Diseases
Dong-Qun Liu, Shuai Lu, Ling-Xiao Zhang, Mei Ji, Shu-Ying Liu, Shao-Wei Wang, Rui-Tian Liu
Therapeutic vaccine is a promising approach in cancer therapy. But tumor-associated antigen peptides have weak immunogenicity and cancer patients are often characterized by immunosuppression and tolerance, leading to less efficiency of immunotherapy. We here successfully developed indoleamine 2, 3-dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2 (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP). YCPs had positive charges with a diameter of approximately 5μm, resulting in selective phagocytosis by APC cells...
January 17, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Eleftherios Pelechas, Paraskevi V Voulgari, Alexandros A Drosos
Rheumatoid arthritis (RA) is an autoimmune disease, which has a negative impact on the ability to perform activities daily. Tumour necrosis factor α (TNF) is a cytokine with diverse cellular effects, and a key regulator of the inflammatory response. ABP 501 is a biosimilar to adalimumab, a TNF inhibitor. Areas covered: In this review, we examined ABP 501, as a biosimilar candidate to adalimumab in the treatment of RA focusing on the available data. Current data indicate that ABP 501 is a highly similar alternative to adalimumab in terms of safety, efficacy, tolerability and immunogenicity...
January 19, 2018: Expert Opinion on Biological Therapy
Melissa R Ryerson, Joanna L Shisler
Modified Vaccinia virus Ankara (MVA) is an attenuated Vaccinia virus (VACV) that is a popular vaccine vector candidate against many different pathogens. Its replication-restricted nature makes it a safe vaccine. However, higher doses or multiple boosts of MVA are necessary to elicit an immune response similar to wild-type VACV. Multiple strategies have been used to create modified MVA viruses that remain safe, but have increased immunogenicity. For example, one common strategy is to delete MVA immunomodulatory proteins in hopes of increasing the host immune response...
January 13, 2018: Virus Research
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