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https://www.readbyqxmd.com/read/28331294/spotlight-on-blisibimod-and-its-potential-in-the-treatment-of-systemic-lupus-erythematosus-evidence-to-date
#1
REVIEW
Aleksander Lenert, Timothy B Niewold, Petar Lenert
B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28327531/porcine-dendritic-cells-as-an-in-vitro-model-to-assess-the-immunological-behaviour-of-streptococcus-suis-subunit-vaccine-formulations-and-the-polarizing-effect-of-adjuvants
#2
Léa Martelet, Sonia Lacouture, Guillaume Goyette-Desjardins, Guy Beauchamp, Charles Surprenant, Marcelo Gottschalk, Mariela Segura
An in vitro porcine bone marrow-derived dendritic cell (DC) culture was developed as a model for evaluating immune polarization induced by adjuvants when administered with immunogens that may become vaccine candidates if appropriately formulated. The swine pathogen Streptococcus suis was chosen as a prototype to evaluate proposed S. suis vaccine candidates in combination with the adjuvants Poly I:C, Quil A ®, Alhydrogel ®, TiterMax Gold ® and Stimune ®. The toll-like receptor ligand Poly I:C and the saponin Quil A ® polarized swine DC cytokines towards a type 1 phenotype, with preferential production of IL-12 and TNF-α...
March 22, 2017: Pathogens
https://www.readbyqxmd.com/read/28323513/transmembrane-tnf-dependent-uptake-of-anti-tnf-antibodies
#3
Arun Deora, Subramanya Hegde, Jacqueline Lee, Chee-Ho Choi, Qing Chang, Cheryl Lee, Lucia Eaton, Hua Tang, Dongdong Wang, David Lee, Mark Michalak, Medha Tomlinson, Qingfeng Tao, Nidhi Gaur, Bohdan Harvey, Shaun McLoughlin, Boris Labkovsky, Tariq Ghayur
TNF-alpha (TNF), a pro-inflammatory cytokine is synthesized as a 26 kDa protein, anchors in the plasma membrane as transmembrane TNF (TmTNF), and is subjected to proteolysis by the TNF-alpha converting enzyme (TACE) to release the 15 kDa form of soluble TNF (sTNF). TmTNF and sTNF interact with two distinct receptors, TNF-R1 (p55) and TNF-R2 (p75), to mediate the multiple biological effects of TNF described to date. Several anti-TNF biologics that bind to both forms of TNF and block their interactions with the TNF receptors are now approved for the treatment of a variety of immune-mediated diseases...
March 21, 2017: MAbs
https://www.readbyqxmd.com/read/28318765/in-vivo-electroporation-in-dna-vlp-prime-boost-preferentially-enhances-hiv-1-envelope-specific-igg2a-neutralizing-antibody-and-cd8-t-cell-responses
#4
Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, Paul Zhou
Although in vivo electroporation (EP) has been utilized to improve immunogenicity in DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectors, no studies on in vivo EP in DNA-VLP prime-boost regimens against HIV-1 have been reported. Previously we developed stably transfected Drosophila S2 clones to produce HIV-1 virus-like particles (VLP) and demonstrated that priming mice twice with DNA plasmids encoding HIV-1 gp120 and gag and boosting twice with HIV-1 VLP (i.e. DDVV immunization) elicited both envelope-specific antibody and envelope and gag-specific CD8 T cell responses...
March 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28317872/preclinical-evaluation-of-the-efficacy-pharmacokinetics-and-immunogenicity-of-js-001-a-programmed-cell-death-protein-1-pd-1-monoclonal-antibody
#5
Jie Fu, Fang Wang, Li-Hou Dong, Jing Zhang, Cheng-Lian Deng, Xue-Li Wang, Xin-Yao Xie, Jing Zhang, Ruo-Xian Deng, Li-Bo Zhang, Hai Wu, Hui Feng, Bo Chen, Hai-Feng Song
JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC50 of 3...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28314076/lactococcus-lactis-carrying-a-dna-vaccine-coding-for-the-esat-6-antigen-increases-il-17-cytokine-secretion-and-boosts-the-bcg-vaccine-immune-response
#6
Vanessa Bastos Pereira, Vanessa Pecini da Cunha, Tatiane Melo Preisser, Bianca Mendes Souza, Meritxell Zurita Turk, Camila Prósperi De Castro, Marcela Santiago Pacheco Azevedo, Anderson Miyoshi
AIMS: A regimen utilizing BCG and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis FnBPA+ (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In the present study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. METHODS AND RESULTS: After immunization, cytokine and immunoglobulin profiles were measured...
March 17, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28306596/biosimilars-implications-for-rheumatoid-arthritis-therapy
#7
Stanley Cohen, Jonathan Kay
PURPOSE OF REVIEW: Abbreviated pathways for the approval of biosimilars have been established in the European Union (EU), the United States, and other countries. Biosimilar TNF inhibitors have been available in South Korea and the EU since 2012 and 2013, respectively, and the first biosimilar infliximab was introduced to the clinic in the United States in November 2016. Five TNF inhibitor biosimilars have now been approved, and many other biosimilars to treat rheumatoid arthritis and other inflammatory diseases are in development...
March 16, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28280494/a-chimera-containing-cd4-and-cd8-t-cell-epitopes-of-the-leishmania-donovani-nucleoside-hydrolase-nh36-optimizes-cross-protection-against-leishmania-amazonesis-infection
#8
Marcus Vinícius Alves-Silva, Dirlei Nico, Alexandre Morrot, Marcos Palatnik, Clarisa B Palatnik-de-Sousa
The Leishmania donovani nucleoside hydrolase (NH36) and NH A34480 of Leishmania amazonensis share 93% of sequence identity. In mice, the NH36 induced protection against visceral leishmaniasis is mediated by a CD4+ T cell response against its C-terminal domain (F3). Besides this CD4+ Th1 response, prevention and cure of L. amazonensis infection require also additional CD8+ and regulatory T-cell responses to the NH36 N-terminal (F1 domain). We investigated if mice vaccination with F1 and F3 domains cloned in tandem, in a recombinant chimera, with saponin, optimizes the vaccine efficacy against L...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28274164/impact-of-immunogenicity-on-response-to-anti-tnf-therapy-in-moderate-to-severe-plaque-psoriasis-results-of-the-predir-study
#9
Mariano Ara-Martín, Pedro Herranz Pinto, Dora Pascual-Salcedo
PURPOSE: This study was conducted to examine the relationship between loss of clinical response to anti-tumor necrosis factor (TNF) therapy and the production of anti-drug antibodies (ADAs) and the potential effects of biologic immunogenicity. MATERIALS AND METHODS: This observational, non-interventional, cross-sectional study included patients with moderate-to-severe plaque psoriasis and secondary failure of adalimumab, etanercept and infliximab who were seen in the clinical practice setting...
March 8, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28261567/mycobacterium-tuberculosis-peptidyl-prolyl-isomerases-are-immunogenic-alter-cytokine-profile-and-aid-in-intracellular-survival
#10
Saurabh Pandey, Deeksha Tripathi, Mohd Khubaib, Ashutosh Kumar, Javaid A Sheikh, Gaddam Sumanlatha, Nasreen Z Ehtesham, Seyed E Hasnain
Mycobacterium tuberculosis (M. tb) has two peptidyl-prolyl isomerases (Ppiases) PpiA and PpiB, popularly known as cyclophilin A and cyclophilin B. The role of cyclophilins in processes such as signaling, cell surface recognition, chaperoning, and heat shock response has been well-documented. We present evidence that M. tb Ppiases modulate the host immune response. ELISA results revealed significant presence of antibodies to M. tb Ppiases in patient sera as compared to sera from healthy individuals. Treatment of THP-1 cells with increasing concentrations of rPpiA, induced secretion of pro-inflammatory cytokines TNF-α and IL-6...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28242071/recombinant-bcg-expressing-a-pspa-pdt-fusion-protein-protects-mice-against-pneumococcal-lethal-challenge-in-a-prime-boost-strategy
#11
Cibelly Goulart, Dunia Rodriguez, Alex I Kanno, Ying-Jie Lu, Richard Malley, Luciana C C Leite
Pneumococcal proteins have been evaluated as genetically-conserved potential vaccine candidates. We have previously demonstrated that a fragment of PspA in fusion with PdT (rPspA-PdT) induced protective immune responses in mice. However, purified proteins have shown poor immunogenicity and often require the combination with strong adjuvants and booster doses. Here, we investigated the use of a Bacillus Calmette-Guérin (BCG) strain, a well-established prophylactic vaccine for tuberculosis with known adjuvant properties, for delivery of the PspA-PdT fusion protein...
February 24, 2017: Vaccine
https://www.readbyqxmd.com/read/28242069/conjugation-of-peg-hexadecane-markedly-increases-the-immunogenicity-of-pneumococcal-polysaccharide-conjugate-vaccine
#12
Xin Chang, Weili Yu, Shaoyang Ji, Lijuan Shen, Aijuan Tan, Tao Hu
Streptococcus pneumoniae is a serious Gram-positive pathogen that can lead to an invasive pneumococcal disease with high mortality rate. Pneumococcal capsular polysaccharide (PS) is a key virulence determinant and its immunogenicity can be increased by conjugation with a carrier protein. However, the PS-specific cellular and humoral immunity of pneumococcal conjugate vaccine needs further improvement. Hexadecane (HD) is an element of lipid that decorates the surface of nearly all microbial classes. Polyethylene glycol (PEG)-HD conjugate (PEG-HD) is soluble and can act as an adjuvant...
February 24, 2017: Vaccine
https://www.readbyqxmd.com/read/28237837/a-novel-dna-vaccine-platform-enhances-neo-antigen-like-t-cell-responses-against-wt1-to-break-tolerance-and-induce-anti-tumor-immunity
#13
Jewell N Walters, Bernadette Ferraro, Elizabeth K Duperret, Kimberly A Kraynyak, Jaemi Chu, Ashley Saint-Fleur, Jian Yan, Hy Levitsky, Amir S Khan, Niranjan Y Sardesai, David B Weiner
Tumor-associated antigens have emerged as important immunotherapeutic targets in the fight against cancer. Germline tumor antigens, such as WT1, Wilms' tumor gene 1, are overexpressed in many human malignancies but have low expression in somatic tissues. Recent vaccination approaches to target WT1 have been hampered by poor in vivo immune potency, likely due to the conserved self-antigen nature of WT1. In this study, we use a novel synthetic micro-consensus SynCon DNA vaccine approach with the goal of breaking tolerance and increasing vaccine immune potency...
February 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28230306/suppression-of-anti-drug-antibodies-to-infliximab-or-adalimumab-with-the-addition-of-an-immunomodulator-in-patients-with-inflammatory-bowel-disease
#14
A S Strik, G R van den Brink, C Ponsioen, R Mathot, M Löwenberg, G R D'Haens
BACKGROUND: Loss of response to anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD) is often caused by anti-drug antibody formation with neutralisation of drug effect. Addition of an immunomodulator has been suggested to reduce immunogenicity, leading to regained response. AIM: To investigate whether addition of an immunomodulator to anti-TNF monotherapy could lead to anti-drug antibody suppression and regained clinical response in IBD patients...
February 23, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28167939/transgenic-eimeria-magna-p%C3%A3-rard-1925-displays-similar-parasitological-properties-to-the-wild-type-strain-and-induces-an-exogenous-protein-specific-immune-response-in-rabbits-oryctolagus-cuniculus-l
#15
Geru Tao, Tuanyuan Shi, Xinming Tang, Donald W Duszynski, Yunzhou Wang, Chao Li, Jingxia Suo, Xiuling Tian, Xianyong Liu, Xun Suo
Rabbit coccidiosis causes great economic losses to world rabbitries. Little work has been done considering genetic manipulation on the etiological agents, rabbit Eimeria spp. In this study, we constructed a transgenic line of Eimeria magna (EmagER) expressing enhanced yellow fluorescent protein (EYFP) and red fluorescent protein (RFP) using regulatory sequences of Eimeria tenella and Toxoplasma gondii. We observed the life cycle of EmagER and confirmed that the transgenic parasites express exogenous proteins targeted to different cellular compartments throughout the entire life cycle...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28160250/thiopurines-and-methotrexate-use-in-ibd-patients-in-a-biologic-era
#16
REVIEW
Gerassimos J Mantzaris
Although we have been living in the era of biologic therapy for several decades, the use of immunomodulators (primarily thiopurines [azathioprine and mercaptopurine] and less so methotrexate) still remains an important component of the inflammatory bowel disease (IBD) pharmaceutical arsenal. Thiopurines as monotherapy exert corticosteroid-sparing effects and can maintain long-term remission in a considerable proportion of patients who have frequent relapses and are or have become mesalazine and/or corticosteroid intolerant or refractory...
March 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28147380/promises-and-dangers-of-combination-therapy
#17
REVIEW
Wolfgang Kruis, Phuong G Nguyen, Julia Morgenstern
The efficiency of the existing methods of treating inflammatory bowel disease (IBD) is limited. There are 2 ways to address this problem - either create new treatment modalities or optimize current therapies. Optimisation may be accomplished by using combinations of established therapeutic strategies. With regard to topically acting compounds such as 5-aminosalicylic acid, combining oral and rectal preparations is a commonly used method. Another commonly used combination is anti-tumor necrosis factor (TNF)-α antibody modalities together with immunosuppressants (thiopurines, methotrexate)...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28130912/effects-on-human-heart-valve-immunogenicity-in-vitro-by-high-concentration-cryoprotectant-treatment
#18
Benjamin A Högerle, Maria Schneider, Katrin Sudrow, Naima Souidi, Meaghan Stolk, Isabella Werner, Anna Biermann, Kelvin G M Brockbank, Ulrich A Stock, Martina Seifert
Previously it was shown that cryopreservation using an ice-free cryopreservation method with the cryoprotectant formulation VS83 beneficially modulated immune reactions in vivo and in vitro when compared with conventionally frozen tissues. In this study, we assessed the impact of a VS83 post-treatment of previously conventionally frozen human tissue on responses of human immune cells in vitro. Tissue punches of treated and non-treated (control) aortic heart valve tissue (leaflets and associated aortic root) were co-cultured for 7 days with peripheral blood mononuclear cells or enriched CD14(+) monocytes...
January 28, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28122644/mtb-specific-lymphocyte-responses-are-impaired-in-tuberculosis-patients-with-pulmonary-cavities
#19
Jun Wang, Yaping Dai, Jun Liu, Yongmei Yin, Hao Pei
OBJECTIVE: Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), is a global health problem. Because the failing immune response in the lung can lead to formation of a pulmonary cavity, this study was designed to clarify MTB-specific lymphocyte responses in TB patients with pulmonary cavities. METHODS: We utilized culture filtrate protein 10 (CFP-10) and early secretory antigenic target 6 (ESAT-6) as immunogenic MTB antigens following overnight stimulation of peripheral blood mononuclear cells (PBMCs)...
January 26, 2017: European Journal of Medical Research
https://www.readbyqxmd.com/read/28110884/tumor-antigen-specific-cd8-t-cells-are-negatively-regulated-by-pd-1-and-tim-3-in-human-gastric-cancer
#20
Xu Lu, Lin Yang, Daxing Yao, Xuan Wu, Jingpo Li, Xuesong Liu, Lijuan Deng, Caiting Huang, Yue Wang, Dan Li, Jingwei Liu
Cytotoxic CD8 T lymphocytes that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally important in eliciting tumor rejection. NY-ESO-1 is a major target of CD8(+) T cell recognition in gastric cancer (GC) and is among the most immunogenic tumor antigens defined to date. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T cell dysfunction may reveal effective strategies for immunotherapy. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1-specific CD8(+) T cells derived from peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) of GC patients...
March 2017: Cellular Immunology
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