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https://www.readbyqxmd.com/read/29774052/therapeutic-drug-monitoring-of-vedolizumab-in-inflammatory-bowel-disease-current-data-and-future-directions
#1
REVIEW
Mark G Ward, Miles P Sparrow, Xavier Roblin
The introduction of vedolizumab, a lymphocyte adhesion inhibitor, has expanded the relatively limited therapeutic armamentarium available for Crohn's disease and ulcerative colitis. Despite its effectiveness, both primary nonresponse and secondary loss of response to vedolizumab do occur, as is observed with the use of anti-tumour necrosis factor (TNF) therapy. Further, in a proportion, onset of efficacy may be relatively slow. A large body of data support an exposure-response relationship with anti-TNF drug levels, which has led to therapeutic drug monitoring becoming incorporated into everyday clinical management...
2018: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29756565/anti-tnf-biosimilars-in-inflammatory-bowel-disease-searching-the-proper-patient-s-profile
#2
Silvio Danese, Gionata Fiorino
Biosimilars of infliximab (CT-P13) are currently approved and available for the same indications as the originator. Some concerns about safety and immunogenicity have risen in the past because of lack of data in IBD. Since 2015, several cohort studies have been conducted in IBD showing that CT-P13 has comparable safety and efficacy profile to the originator, both in adult and pediatric population, either in naïve patients, or even in those who switched from the originator to CT-P13. This review aims to analyze the current literature data in order to define a clear patient profile, to identify those IBD patients who would benefit the most from the use of CT-P13...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29755461/efficient-uptake-of-recombinant-lipidated-survivin-by-antigen-presenting-cells-initiates-antigen-cross-presentation-and-antitumor-immunity
#3
Chen-Yi Chiang, Yi-Jyun Chen, Chiao-Chieh Wu, Shih-Jen Liu, Chih-Hsiang Leng, Hsin-Wei Chen
Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic. Bacteria-derived lipoproteins can activate antigen-presenting cells through their toll-like receptors to enhance immune responses. In this context, lipidated survivin is an attractive candidate for cancer immunotherapy. In the present study, recombinant lipidated human survivin (LSur) was prepared from an Escherichia coli -based system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29752633/clinical-pharmacokinetic-and-pharmacodynamic-considerations-in-the-treatment-of-ulcerative-colitis
#4
REVIEW
Sophie E Berends, Anne S Strik, Mark Löwenberg, Geert R D'Haens, Ron A A Mathôt
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology, probably caused by a combination of genetic and environmental factors. The treatment of patients with active UC depends on the severity, localization and history of IBD medication. According to the classic step-up approach, treatment with 5-aminosalicylic acid compounds is the first step in the treatment of mild to moderately active UC. Corticosteroids, such as prednisolone are used in UC patients with moderate to severe disease activity, but only for remission induction therapy because of side effects associated with long-term use...
May 12, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29751636/design-synthesis-and-evaluation-of-novel-immunomodulatory-small-molecules-targeting-the-cd40%C3%A2-cd154-costimulatory-protein-protein-interaction
#5
Damir Bojadzic, Jinshui Chen, Oscar Alcazar, Peter Buchwald
We report the design, synthesis, and testing of novel small-molecule compounds targeting the CD40⁻CD154 (CD40L) costimulatory interaction for immunomodulatory purposes. This protein-protein interaction (PPI) is a TNF-superfamily (TNFSF) costimulatory interaction that is an important therapeutic target since it plays crucial roles in the activation of T cell responses, and there is resurgent interest in its modulation with several biologics in development. However, this interaction, just as all other PPIs, is difficult to target by small molecules...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29740446/antigenicity-of-leishmania-activated-c-kinase-antigen-lack-in-human-peripheral-blood-mononuclear-cells-and-protective-effect-of-prime-boost-vaccination-with-pci-neo-lack-plus-attenuated-lack-expressing-vaccinia-viruses-in-hamsters
#6
Laura Fernández, Eugenia Carrillo, Lucas Sánchez-Sampedro, Carmen Sánchez, Ana Victoria Ibarra-Meneses, M Angeles Jimenez, Valter Dos Anjos Almeida, Mariano Esteban, Javier Moreno
Leishmania -activated C-kinase antigen (LACK) is a highly conserved protein among Leishmania species and is considered a viable vaccine candidate for human leishmaniasis. In animal models, prime-boost vaccination with LACK-expressing plasmids plus attenuated vaccinia viruses (modified vaccinia Ankara [MVA] and mutant M65) expressing LACK, has been shown to protect against cutaneous leishmaniasis (CL). Further, LACK demonstrated to induce the production of protective cytokines in patients with active CL or cured visceral leishmaniasis, as well as in asymptomatic individuals from endemic areas...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29731461/-diagnosis-and-treatment-of-rheumatoid-arthritis-toward-the-best-practice-the-best-practice-for-tnf-inhibitors
#7
Hideto Kameda
As of February 2018, 5 originator TNF inhibitors(infliximab, etanercept, adalimumab, golimumab and certolizumab pegol)and biosimilar agents of infliximab and etanercept are available for rheumatoid arthritis(RA)in Japan. The effectiveness of TNF inhibitors considerably improves with concomitant methotrexate regardless of their immunogenicity. The Japan College of Rheumatology guideline for TNF inhibitor use in RA has been updated in March 2017 according to recent evidences. During the remission induction phase, maintenance of drug trough level above effective blood concentration is paramount, while the tapering and withdrawal of TNF inhibitors may be considered after achieving sustained remission...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29689371/large-supramolecular-structures-of-33-mer-gliadin-peptide-activate-toll-like-receptors-in-macrophages
#8
M G Herrera, M Pizzuto, C Lonez, K Rott, A Hütten, N Sewald, J-M Ruysschaert, V I Dodero
Gliadin, an immunogenic protein present in wheat, is not fully degraded by humans and after the normal gastric and pancreatic digestion, the immunodominant 33-mer gliadin peptide remains unprocessed. The 33-mer gliadin peptide is found in human faeces and urine, proving not only its proteolytic resistance in vivo but more importantly its transport through the entire human body. Here, we demonstrate that 33-mer supramolecular structures larger than 220nm induce the overexpression of nuclear factor kappa B (NF-κB) via a specific Toll-like Receptor (TLR) 2 and (TLR) 4 dependent pathway and the secretion of pro-inflammatory cytokines such as IP-10/CXCL10 and TNF-α...
April 21, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29673285/tlr-agonist-combinations-that-stimulate-th-type-i-polarizing-responses-from-human-neonates
#9
Naveen Surendran, Andrea Simmons, Michael E Pichichero
Each year millions of neonates die due to vaccine preventable infectious diseases. Our study seeks to develop novel neonatal vaccines and improve immunogenicity of early childhood vaccines by incorporating TLR agonist-adjuvant combinations that overcome the inherent neonatal Th2 bias and stimulate Th1 polarizing response from neonatal APCs. We systematically stimulated cord blood mononuclear cells with single and multiple combinations of TLR agonists and measured levels of IL-12p70, IFN-γ, IFN-α, IL-10, IL-13, TNF-α, IL-6 and IL-1β from cell culture supernatants...
January 1, 2018: Innate Immunity
https://www.readbyqxmd.com/read/29649688/recombinant-outer-membrane-protein-25c-from-brucella-abortus-induces-th1-and-th2-mediated-protection-against-brucella-abortus-infection-in-mouse-model
#10
Soumya Paul, Bhavani V Peddayelachagiri, Sowmya Nagaraj, Joseph J Kingston, Harsh V Batra
Development of a safe and efficacious vaccine for brucellosis is a long standing challenge for scientists. Recognizing potential antigens towards developing vaccine candidate is crucial. Omp25c, a porin protein of Brucella, is a paralog of two previously identified promising vaccine candidates namely, Omp25 and Omp31, with notable sequence identity. Also, Omp25c is conserved in all major Brucella species. This highlights the possibility of employing this protein in multivalent subunit vaccine based approach of Brucella management...
April 9, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29627232/protective-efficacy-of-recombinant-bcg-over-expressing-protective-stage-specific-antigens-of-mycobacterium-tuberculosis
#11
Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J Britton, James A Triccas
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, yet current control strategies, including the existing BCG vaccine, have had little impact on disease control. CysVac2, a fusion protein comprising stage-specific Mycobacterium tuberculosis antigens, provided superior protective efficacy against chronic M. tuberculosis infection in mice, compared to BCG. To determine if the delivery of CysVac2 in the context of BCG could improve BCG-induced immunity and protection, we generated a recombinant strain of BCG overexpressing CysVac2 (rBCG:CysVac2)...
April 4, 2018: Vaccine
https://www.readbyqxmd.com/read/29615127/inflammatory-licensed-equine-mscs-are-chondroprotective-and-exhibit-enhanced-immunomodulation-in-an-inflammatory-environment
#12
Jennifer M Cassano, Lauren V Schnabel, Margaret B Goodale, Lisa A Fortier
BACKGROUND: Inflammatory licensed mesenchymal stem cells (MSCs) have the ability to promote functional tissue repair. This study specifically sought to understand how the recipient tissue environment reciprocally affects MSC function. Inflammatory polarized macrophages, modeling an injured tissue environment, were exposed to licensed MSCs, and the resultant effects of MSC immunomodulation and functionality of the MSC secretome on chondrocyte homeostasis were studied. METHODS: Inflammatory licensed MSCs were generated through priming with either IFN-γ or polyinosinic:polycytidylic acid (poly I:C)...
April 3, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29614084/identification-of-hla-drb1-association-to-adalimumab-immunogenicity
#13
Mohan Liu, Jacob Degner, Justin Wade Davis, Kenneth B Idler, Ahmed Nader, Nael M Mostafa, Jeffrey F Waring
Anti-drug antibody formation occurs with most biological agents across disease states, but the mechanism by which they are formed is unknown. The formation of anti-drug antibodies to adalimumab (AAA) may decrease its therapeutic effects in some patients. HLA alleles have been reported to be associated with autoantibody formation against interferons and other TNF inhibitors, but not adalimumab. We analyzed samples from 634 subjects with either rheumatoid arthritis (RA) or hidradenitis suppurativa (HS): 37 subjects (17 RA and 20 HS) developed AAA (AAA+) during adalimumab treatment and 597 subjects (348 RA, 249 HS) did not develop AAA (AAA-) during the clinical trials...
2018: PloS One
https://www.readbyqxmd.com/read/29602704/sequential-pulmonary-immunization-with-heterologous-recombinant-influenza-a-virus-tuberculosis-vaccines-protects-against-murine-m-tuberculosis-infection
#14
H Muflihah, M Flórido, L C W Lin, Y Xia, J A Triccas, J Stambas, W J Britton
Tuberculosis (TB) infection affects a quarter of the global population resulting in a large burden of TB disease and mortality. The long-term control of TB requires vaccines with greater efficacy and durability than the current Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary immunization may increase and prolong immunity at the site of Mycobacterium tuberculosis infection. We have investigated recombinant influenza A viruses (rIAVs) expressing the p25 CD4+ T cell epitope of M. tuberculosis Ag85B240-254 for single and sequential immunization against M...
March 27, 2018: Vaccine
https://www.readbyqxmd.com/read/29601585/trypanosoma-cruzi-80-kda-prolyl-oligopeptidase-tc80-as-a-novel-immunogen-for-chagas-disease-vaccine
#15
Augusto E Bivona, Andrés Sánchez Alberti, Marina N Matos, Natacha Cerny, Alejandro C Cardoso, Celina Morales, Germán González, Silvia I Cazorla, Emilio L Malchiodi
BACKGROUND: Chagas disease, also known as American Trypanosomiasis, is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection. Despite of being endemic on 21 Latin-American countries, Chagas disease has become a global concern due to migratory movements. Unfortunately, available drugs for the treatment have several limitations and they are generally administered during the chronic phase of the infection, when its efficacy is considered controversial...
March 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29570096/smart-self-tightening-surgical-suture-from-tough-bio-based-hyperbranched-polyurethane-reduced-carbon-dot-nanocomposite
#16
Rituparna Duarah, Yogendra P Singh, Prerak Gupta, Biman B Mandal, Niranjan Karak
Design and fabrication of a smart bio-based polymeric material with potent biocompatibility and high performance still remain a challenge in biomedical realm. In this context, potential smart suture was fabricated from starch modified hyperbranched polyurethane (HPU) nanocomposites with different weight percentages of reduced carbon dot for the first time. The desired mechanical (tensile strength: 32.14 MPa, elongation at break: 1576% and toughness 439.28 MJ m-3) and thermal (286 °C) attributes of the suture were achieved with 2 weight% of RCD in HPU matrix...
March 23, 2018: Biomedical Materials
https://www.readbyqxmd.com/read/29566772/platelet-lysate-as-a-novel-serum-free-media-supplement-for-the-culture-of-equine-bone-marrow-derived-mesenchymal-stem-cells
#17
Maria C Naskou, Scarlett M Sumner, Anna Chocallo, Hannah Kemelmakher, Merrilee Thoresen, Ian Copland, Jacques Galipeau, John F Peroni
BACKGROUND: Mesenchymal stem cells (MSCs) produced for clinical purposes rely on culture media containing fetal bovine serum (FBS) which is xenogeneic and has the potential to significantly alter the MSC phenotype, rendering these cells immunogenic. As a result of bovine-derived exogenous proteins expressed on the cell surface, MSCs may be recognized by the host immune system as non-self and be rejected. Platelet lysate (PL) may obviate some of these concerns and shows promising results in human medicine as a possible alternative to FBS...
March 22, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29559126/biophysical-and-immunological-characterization-of-the-esx-4-system-esat-6-family-proteins-rv3444c-and-rv3445c-from-mycobacterium-tuberculosis-h37rv
#18
Himanshu Pandey, Farheen Fatma, Shivraj M Yabaji, Meera Kumari, Sarita Tripathi, Kanchan Srivastava, Dinesh K Tripathi, Surya Kant, Kishore K Srivastava, Ashish Arora
The ESAT-6 family proteins of Mycobacterium tuberculosis are regarded as the key mediators in mycobacterial virulence and are largely considered as antigens that can improve TB vaccines and diagnostics. We have characterized Rv3444c and Rv3445c proteins of the ESX-4 system of ESAT-6 family of M. tuberculosis H37Rv, and have experimentally established that these two proteins interact to form a heterodimeric complex. Complex formation resulted in induction of α-helical conformation and stability against chemical denaturation...
March 2018: Tuberculosis
https://www.readbyqxmd.com/read/29550192/immune-response-elicited-by-two-rbcg-strains-devoid-of-genes-involved-in-c-di-gmp-metabolism-affect-protection-versus-challenge-with-m-tuberculosis-strains-of-different-virulence
#19
Cristian Alfredo Segura-Cerda, Michel de Jesús Aceves-Sánchez, Brenda Marquina-Castillo, Dulce Mata-Espinoza, Jorge Barrios-Payán, Perla Jazmín Vega-Domínguez, César Pedroza-Roldán, Jorge Bravo-Madrigal, Alba Adriana Vallejo-Cardona, Rogelio Hernández-Pando, Mario Alberto Flores-Valdez
Pellicles, a type of biofilm, have gathered a renewed interest in the field of tuberculosis as a structure that mimics some characteristics occurring during M. tuberculosis infection, such as antibiotic recalcitrance and chronicity of infection, and as a source of antigens for humoral response in infected guinea pigs. In other bacteria, it has been well documented that the second messenger c-di-GMP modulates the transition from planktonic cells to biofilm formation. In this work, we used the live vaccine Mycobacterium bovis BCG to determine whether deletion of genes involved in c-di-GMP metabolism would affect interaction with macrophages, capacity to induce immune response in a murine cell line and mice, and how the protein profile was modified when grown as surface pellicles...
March 14, 2018: Vaccine
https://www.readbyqxmd.com/read/29538682/immunogenicity-of-quadrivalent-influenza-vaccine-for-patients-with-inflammatory-bowel-disease-undergoing-immunosuppressive-therapy
#20
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
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