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https://www.readbyqxmd.com/read/28648866/cytokines-in-immunogenic-cell-death-applications-for-cancer-immunotherapy
#1
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...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28647488/autoreactivity-to-malondialdehyde-modifications-in-rheumatoid-arthritis-is-linked-to-disease-activity-and-synovial-pathogenesis
#2
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
https://www.readbyqxmd.com/read/28643827/anti-oxidant-and-immune-modulatory-properties-of-sulfated-alginate-derivatives-on-human-chondrocytes-and-macrophages
#3
Anne Kerschenmeyer, Øystein Arlov, Vera Malheiro, Matthias Steinwachs, Markus Rottmar, Katharina Maniura-Weber, Gemma Palazzolo, Marcy Zenobi-Wong
Degeneration of articular cartilage represents one of the most common causes of pain and disability in our aging society. Current treatments only address the symptoms of joint disease, but not their underlying causes which include oxidative stress and inflammation in cartilage and surrounding tissues. Sulfated biopolymers that mimic aspects of the native extracellular environment of cartilage are recently gaining interest as a means to slow the inflammatory events responsible for tissue degeneration. Here we show that the natural polysaccharide alginate and particularly its sulfated derivatives have potent anti-oxidant, anti-inflammatory and anti-immunogenic properties in vitro...
June 23, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28622097/evolution-of-cytokines-and-inflammatory-biomarkers-during-infliximab-induction-therapy-and-the-impact-of-inflammatory-burden-on-primary-response-in-patients-with-crohn-s-disease
#4
Thomas Billiet, Isabelle Cleynen, Vera Ballet, Karolien Claes, Fred Princen, Sharat Singh, Marc Ferrante, Gert Van Assche, Ann Gils, Severine Vermeire
OBJECTIVE: Primary non-response to infliximab in Crohn's disease is still incompletely understood. Our aim was to further characterize the role of inflammatory burden during infliximab induction therapy. MATERIALS AND METHODS: We studied a well-characterized cohort of 201 anti-TNF naive Crohn's disease patients treated with infliximab 5mg/kg at week 0, 2, 6 and 14 who had serum samples drawn just before every infusion. All serum samples were analyzed for CRP, albumin, TNF, IFN-γ, IL-6, IL-8, IL-10, infliximab trough concentrations (in-house-developed ELISA) and antibodies to infliximab (HMSA, Prometheus Laboratories Inc...
June 16, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28620588/immunogenicity-and-protective-efficacy-of-a-fusion-protein-tuberculosis-vaccine-combining-five-esx-family-proteins
#5
Zhi-Hao Xiang, Rui-Feng Sun, Chen Lin, Fu-Zeng Chen, Jun-Tao Mai, Yu-Xiao Liu, Zi-Yan Xu, Lu Zhang, Jun Liu
One strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on T cell antigens. In this study, we have evaluated the vaccine potential of a fusion protein combining EsxB, EsxD, EsxG, EsxU, and EsxM of Mycobacterium tuberculosis (M. tb). This recombinant protein, named BM, was expressed in and purified from Escherichia coli. Immunization of C57BL/6 mice with purified BM protein formulated in Freund's incomplete adjuvant induced the production of Th1 cytokines (IFN-γ, TNF, and IL-2) and multifunctional CD4(+) T cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28619678/april-taci-axis-is-dispensable-for-the-immune-response-to-rabies-vaccination
#6
Shannon L Haley, Evgeni P Tzvetkov, Andrew G Lytle, Kishore R Alugupalli, Joseph R Plummer, James P McGettigan
There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens...
June 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28608166/abatacept-a-review-in-rheumatoid-arthritis
#7
Hannah A Blair, Emma D Deeks
The biological DMARD (bDMARD) abatacept (Orencia(®)), a recombinant fusion protein, selectively modulates a co-stimulatory signal necessary for T-cell activation. In the EU, abatacept is approved for use in patients with highly active and progressive rheumatoid arthritis (RA) not previously treated with methotrexate. Abatacept is also approved for the treatment of moderate to severe active RA in patients with an inadequate response to previous therapy with at least one conventional DMARD (cDMARD), including methotrexate or a TNF inhibitor...
June 12, 2017: Drugs
https://www.readbyqxmd.com/read/28588103/mycobacteriumtuberculosis-rv3615c-is-a-highly-immunodominant-antigen-and-specifically-inducespotent-th1-type-immune-responses-in-tuberculosis-pleurisy
#8
Jiangping Li, Juan Shen, Suihua Lao, Xiaomin Li, Jie Liu, Changyou Wu
T-cell responses have been demonstrated essential for preventing M.tb infection. The Th1-cytokines produced by T cells, such as INF-γ, IL-2 and TNF-α, not only limit the invasion of M.tb but also eliminate the pathogen at site of infection. BCG is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components in addition to those expressed in BCG and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity...
June 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28584008/crucial-role-for-immune-complexes-but-not-fcrn-in-immunization-against-anti-tnf-%C3%AE-antibodies-after-a-single-injection-in-mice
#9
Christophe Arnoult, Guillaume Brachet, Diana Cadena Castaneda, Nicolas Azzopardi, Christophe Passot, Celine Desvignes, Gilles Paintaud, Nathalie Heuzé-Vourc'h, Hervé Watier, Valérie Gouilleux-Gruart
The immunogenicity of infliximab and adalimumab is a major concern because patients may develop Abs also called antidrug Abs (ADA), directed against these anti-TNF-α Abs after just a few weeks of treatment. These ADAs can lead to a decrease in biologic concentration, which is associated with lower treatment efficacy. Our aim was to study the involvement of immune complexes and neonatal Fc receptor (FcRn) in the emergence of ADAs in the case of anti-TNF-α Abs. Wild type and FcRn knockout mice were injected once with either infliximab or adalimumab, alone or preincubated with TNF-α...
June 5, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28562666/quantitative-analysis-of-the-cd4-t-cell-response-to-therapeutic-antibodies-in-healthy-donors-using-a-novel-t-cell-pbmc-assay
#10
Heidi S Schultz, Stine Louise Reedtz-Runge, B Thomas Bäckström, Kasper Lamberth, Christian R Pedersen, Anne M Kvarnhammar
Many biopharmaceuticals (BPs) are known to be immunogenic in the clinic, which can result in modified pharmacokinetics, reduced efficacy, allergic reactions and anaphylaxis. During recent years, several technologies to predict immunogenicity have been introduced, but the predictive value is still considered low. Thus, there is an unmet medical need for optimization of such technologies. The generation of T cell dependent high affinity anti-drug antibodies plays a key role in clinical immunogenicity. This study aimed at developing and evaluating a novel in vitro T cell:PBMC assay for prediction of the immunogenicity potential of BPs...
2017: PloS One
https://www.readbyqxmd.com/read/28561325/assays-for-infliximab-drug-levels-and-antibodies-a-matter-of-scales-and-categories
#11
L Bader, S M Solberg, S H Kaada, N Bolstad, D J Warren, S Gavasso, C G Gjesdal, C A Vedeler
Immunogenicity is a frequent cause of secondary non-response to tumor necrosis factor (TNF) inhibitors. Drug level measurement and detection of anti-drug antibodies has been shown to be cost-effective and clinically relevant, and a large number of assays are available for these purposes. It is, however, difficult to compare assays and translate results into clinical meaningful information due to different methodological approaches and a lack of assay standardization. We have analyzed infliximab drug levels and anti-drug antibodies in 107 patient samples using enzyme-linked immunoassays (ELISA), immunofluorometric assays (IFMA), and reporter gene assays (RGA) for drug and for antibody...
May 31, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28553360/in-vivo-immunogenic-response-to-allogeneic-mesenchymal-stem-cells-and-the-role-of-preactivated-mesenchymal-stem-cells-cotransplanted-with-allogeneic-islets
#12
Régis Linhares Oliveira, Pedro Cesar Chagastelles, Patrícia Sesterheim, Patricia Pranke
Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into cells from the mesenchymal lineage. The hypoimmunogenic characteristic of MSCs has encouraged studies using allogeneic MSCs for the treatment of autoimmune diseases and inflammatory conditions. Promising preclinical results and the safety of allogeneic MSC transplantation have created the possibility of "off-the-shelf" clinical application of allogeneic cells. This study has aimed to evaluate the survival of untreated and IFN-γ- and TNF-α-treated (preactivated) allogeneic MSCs transplanted under the kidney capsule of immunocompetent mice together with the role of preactivated MSCs after cotransplantation with allogeneic islets...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28552512/immune-response-to-pneumococcal-conjugate-vaccine-in-patients-with-systemic-vasculitis-receiving-standard-of-care-therapy
#13
Per Nived, Johanna Nagel, Tore Saxne, Pierre Geborek, Göran Jönsson, Lillemor Skattum, Meliha C Kapetanovic
AIM: To study the effect of standard of care therapy on antibody response and functionality following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in patients with primary systemic vasculitis compared to healthy controls. METHODS: 49 patients with vasculitis and 49 controls received a single dose (0.5ml) PCV13 intramuscularly. Ongoing treatments: azathioprine (AZA; n=11), cyclophosphamide (CYC; n=6), methotrexate (MTX; n=9), rituximab (n=3); anti-TNF (n=2), mycophenolate mofetil (n=2), prednisolone alone (n=15) and no active treatment (n=2)...
June 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28530164/biocompatibility-of-intensified-decellularized-equine-carotid-arteries-in-a-rat-subcutaneous-implantation-model-and-in-a-human-in-vitro-model
#14
Niklas Jeinsen, Lavinia Maegel, Danny Jonigk, Melanie Klingenberg, Axel Haverich, Mathias Wilhelmi, Ulrike Böer
Limited biocompatibility of decellularized scaffolds is an ongoing challenge in tissue engineering. We recently demonstrated that intensified detergent-based decellularization of equine carotid artery (dEACintens) removed residual cellular molecules from the scaffold more efficiently than a conventional decellularization (dEACcon) though this approach did not eliminate its immunogenicity entirely. CCN1 has been shown to improve biocompatibility of dEACcon in a sheep model. Here, we tested the biocompatibility of dEACintens and dEACcon with or without CCN1-coating after subcutaneous implantation in rats for up to 12 weeks...
May 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28523450/a-review-of-the-clinical-pharmacokinetics-pharmacodynamics-and-immunogenicity-of-vedolizumab
#15
REVIEW
Maria Rosario, Nathanael L Dirks, Catherine Milch, Asit Parikh, Michael Bargfrede, Tim Wyant, Eric Fedyk, Irving Fox
Vedolizumab is a humanized anti-α4β7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α4β7-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), vedolizumab is administered as a 300 mg intravenous infusion. Vedolizumab undergoes a rapid, saturable, non-linear, target-mediated elimination process at low concentrations and a slower, linear, non-specific elimination process at higher concentrations...
May 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28513424/a-review-of-six-methods-for-monitoring-infliximab-concentrations-and-antibodies-to-infliximab%C3%A2
#16
Fang Cao, Hailong Cao, Xiaocang Cao
Anti-TNF-α therapy, such as infliximab (IFX), has profoundly changed treatment to induce and maintain remission for inflammatory bowel diseases patients who do not respond to conventional therapies. Unfortunately, IFX, as a chimeric protein, is potentially immunogenic, and antibodies to infliximab (ATI) may interfere with the pharmacodynamics and pharmacokinetics of the drug, thus resulting in a loss of response for a substantial proportion of patients. The clinical efficacy of IFX is correlated with the levels of IFX and ATI...
May 17, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28502609/switching-from-originator-infliximab-to-biosimilar-ct-p13-compared-with-maintained-treatment-with-originator-infliximab-nor-switch-a-52-week-randomised-double-blind-non-inferiority-trial
#17
Kristin K Jørgensen, Inge C Olsen, Guro L Goll, Merete Lorentzen, Nils Bolstad, Espen A Haavardsholm, Knut E A Lundin, Cato Mørk, Jørgen Jahnsen, Tore K Kvien
BACKGROUND: TNF inhibitors have improved treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity. METHODS: The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up...
May 11, 2017: Lancet
https://www.readbyqxmd.com/read/28489423/is-rheumatoid-arthritis-associated-with-reduced-immunogenicity-of-the-influenza-vaccination-a-systematic-review-and-meta-analysis
#18
Yafang Huang, Huili Wang, Wilson W S Tam
OBJECTIVE: To determine whether immunogenicity and safety of the influenza vaccination in rheumatoid arthritis (RA) patients are significantly different from those in a healthy population. METHODS: PubMed, MEDLINE, Embase, Cochrane Library and Web of Science were searched on 31 August 2016. Studies were included when they met the inclusion criteria. Two reviewers independently extracted data on study characteristics, methodological quality and outcomes. The primary outcome was seroprotection (SP) rate after immunization...
June 7, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28487429/rationally-designed-tlr4-ligands-for-vaccine-adjuvant-discovery
#19
Kelsey A Gregg, Erin Harberts, Francesca M Gardner, Mark R Pelletier, Corinne Cayatte, Li Yu, Michael P McCarthy, Jason D Marshall, Robert K Ernst
Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A) are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC) as a method to generate rationally designed, functionally diverse lipid A...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28476676/protective-efficacy-of-cationic-plga-microspheres-loaded-with-dna-vaccine-encoding-the-sip-gene-of-streptococcus-agalactiae-in-tilapia
#20
Yan-Ping Ma, Hao Ke, Zhi-Ling Liang, Jiang-Yao Ma, Le Hao, Zhen-Xing Liu
Streptococcus agalactiae (S. agalactiae) is an important fish pathogen, which has received more attention in the past decade due to the increasing economic losses in the tilapia industry worldwide. As existing effective vaccines of S. agalactiae in fish have obvious disadvantage, to select immunoprotective antigens and package materials would undoubtedly contribute to the development of novel oral vaccines. In the present study, surface immunogenic protein (sip) was selected from the S. agalactiae serovar I a genomes as immunogenic protein in DNA vaccine form with cationic chitosan and biodegradable and biocompatible PLGA...
May 2, 2017: Fish & Shellfish Immunology
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