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https://www.readbyqxmd.com/read/29150961/modulation-of-igg1-immunoeffector-function-by-glycoengineering-of-the-gdp-fucose-biosynthesis-pathway
#1
Ronan M Kelly, Ronald L Kowle, Zhirui Lian, Beth A Strifler, Derrick R Witcher, Bhavin S Parekh, Tongtong Wang, Christopher C Frye
Cross-linking of the Fcγ receptors expressed on the surface of hematopoietic cells by IgG immune complexes triggers the activation of key immune effector mechanisms, including antibody-dependent cell mediated cytotoxicity (ADCC). A conserved N-glycan positioned at the N-terminal region of the IgG CH 2 domain is critical in maintaining the quaternary structure of the molecule for Fcγ receptor engagement. The removal of a single core fucose residue from the N-glycan results in a considerable increase in affinity for FcγRIIIa leading to an enhanced receptor-mediated immunoeffector function...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29142944/atypical-antiglomerular-basement-membrane-disease-with-igg1-%C3%AE%C2%BA-staining
#2
Jehan Z Bahrainwala, M Barry Stokes, Afshin K Hannani, Jonathan J Hogan
No abstract text is available yet for this article.
January 2017: KI Reports
https://www.readbyqxmd.com/read/29140105/durvalumab-in-non-small-cell-lung-cancer-patients-current-developments
#3
Laura Mezquita, David Planchard
Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population. Durvalumab is under evaluation in early, locally advanced and advanced disease as monotherapy and combined with ICIs, targeted therapies, chemotherapy and radiotherapy...
November 15, 2017: Future Oncology
https://www.readbyqxmd.com/read/29138497/rapid-purification-of-human-bispecific-antibodies-via-selective-modulation-of-protein-a-binding
#4
Adam Zwolak, Catherine N Leettola, Susan H Tam, Dennis R Goulet, Mehabaw G Derebe, Jose R Pardinas, Songmao Zheng, Rose Decker, Eva Emmell, Mark L Chiu
Methods to rapidly generate high quality bispecific antibodies (BsAb) having normal half-lives are critical for therapeutic programs. Here, we identify 3 mutations (T307P, L309Q, and Q311R or "TLQ") in the Fc region of human IgG1 which disrupt interaction with protein A while enhancing interaction with FcRn. The mutations are shown to incrementally alter the pH at which a mAb elutes from protein A affinity resin. A BsAb comprised of a TLQ mutant and a wild-type IgG1 can be efficiently separated from contaminating parental mAbs by differential protein A elution starting from either a) purified parental mAbs, b) in-supernatant crossed parental mAbs, or c) co-transfected mAbs...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138085/in-silico-design-cloning-expression-and-immunologic-evaluation-of-ed-fusion-protein-of-nt-h-influenzae
#5
Ava Behrouzi, Saeid Bouzari, Mana Oloomi, Abolfaz Fateh, Farzam Vaziri, Parviz Afrough, Amir Amanzadeh, Seyed Davar Siadat
Infections due to nontypeable Haemophilus influenzae (NTHi) are important causes of child mortality throughout the world. Given the lack of effective vaccines for these strains and the spread and prevalence of these infections in the world, it is necessary to design novel vaccine candidates against these strains. D and E proteins are conserved membrane-specific lipoproteins among encapsulated and non-encapsulated H. influenza strains, which, according to the exposure surface and conservation degree between both strains, can be considered as vaccine candidates suitable for studies...
November 11, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29137301/antitumor-efficacy-of-triple-monoclonal-antibody-inhibition-of-epidermal-growth-factor-receptor-egfr-with-mm151-in-egfr-dependent-and-in-cetuximab-resistant-human-colorectal-cancer-cells
#6
Stefania Napolitano, Giulia Martini, Erika Martinelli, Carminia Maria Della Corte, Floriana Morgillo, Valentina Belli, Claudia Cardone, Nunzia Matrone, Fortunato Ciardiello, Teresa Troiani
Purpose: We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design: MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM151 with irinotecan (induction therapy) followed by MM151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135256/improved-solution-state-properties-of-monoclonal-antibodies-by-targeted-mutations
#7
Alexander B Kuhn, Sebastian Kube, Anne R Karow-Zwick, Daniel Seeliger, Patrick Garidel, Michaela Blech, Lars V Schäfer
Monoclonal antibody (mAb) based therapeutics often require high concentration formulations. Unfortunately, highly concentrated antibody solutions often have biophysical properties that are disadvantageous for therapeutic development, such as high viscosity, solubility limitations, precipitation issues, or liquid-liquid phase separation. In this work, we present a computational rational design principle for improving the thermodynamic stability of mAb solutions through targeted point mutations. Two publicly available IgG1 monoclonal antibodies that exhibit high viscosity at high concentrations were used as model systems...
November 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29133549/pharmacokinetics-and-exposure-response-analysis-of-rg7667-a-combination-of-two-anti-cytomegalovirus-monoclonal-antibodies-in-a-phase-2a-randomized-trial-to-prevent-cytomegalovirus-infection-in-high-risk-kidney-transplant-recipients
#8
Rong Deng, Yehong Wang, Mauricio Maia, Tracy Burgess, Jacqueline M McBride, X Charlene Liao, Jorge A Tavel, William D Hanley
BACKGROUND: RG7667, a novel combination of two anti-cytomegalovirus (CMV) monoclonal IgG1 antibodies (MCMV5322A and MCMV3068A), was designed to block CMV entry into host cells. It was developed as a potential therapy for preventing CMV infection and disease in transplant recipients. METHODS: In a Phase 2a trial in CMV-seronegative recipients of kidney transplants from CMV-seropositive donors, RG7667 was assessed for preventing CMV infection. Patients received 4 intravenous doses of RG7667 (10 mg/kg of each antibody, n=60) or placebo (n=60) at time of transplant, and 1, 4, and 8 weeks post transplant...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29132070/sixteen-year-history-of-rituximab-therapy-for-1085-pemphigus-vulgaris-patients-a-systematic-review
#9
REVIEW
Soheil Tavakolpour, HamidReza Mahmoudi, Kamran Balighi, Robabeh Abedini, Maryam Daneshpazhooh
Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin and mucous membranes. Recently, rituximab, a chimeric IgG1 monoclonal antibody which targets the CD20 molecules have been regarded as a promising treatment for PV. In this study, a systematic review was conducted to conclude on how and which PV patients could benefit from rituximab infusion. Search in PubMed results in 114 relevant studies, which met the criteria...
November 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29130606/oral-administration-of-lactobacillus-plantarum-cjlp133-and-cjlp243-alleviates-birch-pollen-induced-allergic-rhinitis-in-mice
#10
S-P Choi, H-N Oh, C-Y Choi, H Ahn, H S Yun, Y M Chung, B Kim, S J Lee, T Chun
AIMS: In this study, we evaluated the therapeutic efficacy of selected probiotics in a mouse model of birch pollen (BP)-induced allergic rhinitis. METHODS AND RESULTS: Oral administration of lactobacillus plantarum CJLP133 and CJLP243 ameliorated the symptoms of BP-induced allergic rhinitis by reducing airway hyperresponsiveness (AHR), and both the histological scores and the number of infiltrated cells in the nasal cavities and lungs. Compared with those from vehicle-treated mice, bronchoalveolar lavage (BAL) fluid and draining lymph node samples from CJLP133 and CJLP243-administrated mice showed diminished numbers of immune cells, increased secretion of a Th1-type cytokine (IFN-γ), and decreased production of Th2-type cytokines (IL-4, IL-5 and IL-13)...
November 12, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29130480/antidesmoglein-1-and-3-antibodies-in-healthy-subjects-of-a-population-in-the-peruvian-high-amazon
#11
Willy Ramos, Jesús Díaz, Ericson L Gutierrez, Jose S Lazarte, Mary C Bohnett, Gerardo Ronceros, Alex G Ortega-Loayza
BACKGROUND: The objective of this study was to determine the presence of anti-Dsg1 and Dsg3 antibodies in healthy subjects of the high Peruvian Amazon (Tuemal, Rodriguez de Mendoza province, department of Amazonas) to establish the theoretical presence of environmental factors or triggers in the area. MATERIALS AND METHODS: Cross-sectional study. The study population included persons of any age or gender, clinically healthy, who were evaluated by a dermatologist to confirm the absence of blistering diseases...
November 11, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/29127147/igg1-is-required-for-optimal-protection-after-immunization-with-the-purified-porin-ompd-from-salmonella-typhimurium
#12
Yang Zhang, Coral Dominguez-Medina, Nicola J Cumley, Jennifer N Heath, Sarah J Essex, Saeeda Bobat, Anna Schager, Margaret Goodall, Sven Kracker, Christopher D Buckley, Robin C May, Robert A Kingsley, Calman A MacLennan, Constantino López-Macías, Adam F Cunningham, Kai-Michael Toellner
In mice, the IgG subclass induced after Ag encounter can reflect the nature of the Ag. Th2 Ags such as alum-precipitated proteins and helminths induce IgG1, whereas Th1 Ags, such as Salmonella Typhimurium, predominantly induce IgG2a. The contribution of different IgG isotypes to protection against bacteria such as S. Typhimurium is unclear, although as IgG2a is induced by natural infection, it is assumed this isotype is important. Previously, we have shown that purified S. Typhimurium porins including outer membrane protein OmpD, which induce both IgG1 and IgG2a in mice, provide protection to S...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29123241/toxoplasma-gondii-tachyzoite-extract-acts-as-a-potent-immunomodulator-against-allergic-sensitization-and-airway-inflammation
#13
Mirjana Drinić, Angelika Wagner, Priya Sarate, Christian Zwicker, Elke Korb, Gerhard Loupal, Roman Peschke, Anja Joachim, Ursula Wiedermann, Irma Schabussova
Epidemiological and experimental studies have shown an inverse relationship between infections with certain parasites and a reduced incidence of allergic diseases. We and others have shown that infection with Toxoplasma gondii prevents the development of allergy in mice. To establish whether this beneficial effect could be recapitulated by soluble products of this parasite, we tested an extract derived from T. gondii tachyzoites. Immunization of BALB/c mice with tachyzoites lysate antigen (TLA) elicited mixed Th1/Th2 responses...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119245/development-and-characterisation-of-a-novel-glucagon-like-peptide-1-receptor-antibody
#14
Emma K Biggs, Lihuan Liang, Jacqueline Naylor, Shimona Madalli, Rachel Collier, Matthew P Coghlan, David J Baker, David C Hornigold, Peter Ravn, Frank Reimann, Fiona M Gribble
AIMS/HYPOTHESIS: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo...
November 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/29111437/a-new-reliable-transposable-and-cost-effective-assay-for-absolute-quantification-of-total-plasmatic-bevacizumab-by-lc-ms-ms-in-human-plasma-comparing-two-internal-standard-calibration-approaches
#15
Rachel Legeron, Fabien Xuereb, Stephane Chaignepain, Alain-Pierre Gadeau, Stephane Claverol, Jean-William Dupuy, Sarah Djabarouti, Thierry Couffinhal, Jean-Marie Schmitter, Dominique Breilh
The quantification of monoclonal antibodies (mAbs) such as bevacizumab, a recombinant humanized immunoglobulin G1 (hIgG1), in biological fluids, is an essential prerequisite to any pharmacokinetic preclinical and clinical study. To date, reference techniques used to quantify mAbs rely on enzyme-linked immunosorbent assay (ELISA) lacking specificity. Furthermore, the commercially available ELISA kit to quantify bevacizumab in human plasma only assesses the free fraction of the drug. However, the conditions of storage and analysis of plasma samples could alter the physiological equilibrium between the free, bound and partially bound forms of bevacizumab and this could result in over- or underestimation of drug concentration...
October 23, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29110285/chemical-and-biophysical-characteristics-of-monoclonal-antibody-solutions-containing-aggregates-formed-during-metal-catalyzed-oxidation
#16
Linda O Narhi, Quanzhou Luo, Jette Wypych, Riccardo Torosantucci, Andrea Hawe, Kiyoshi Fujimori, Yasser Nashed-Samuel, Vibha Jawa, Marisa K Joubert, Wim Jiskoot
PURPOSE: To physicochemically characterize and compare monoclonal antibody (mAb) solutions containing aggregates generated via metal catalyzed oxidation (MCO). METHODS: Two monoclonal IgG2s (mAb1 and mAb2) and one monoclonal IgG1 (rituximab) were exposed to MCO with the copper/ascorbic acid oxidative system, by using several different methods. The products obtained were characterized by complementary techniques for aggregate and particle analysis (from oligomers to micron sized species), and mass spectrometry methods to determine the residual copper content and chemical modifications of the proteins...
November 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/29109124/endogenous-calcitriol-synthesis-controls-the-humoral-ige-response-in-mice
#17
Juliane Lindner, Sebastian Rausch, Sandra Treptow, Kerstin Geldmeyer-Hilt, Tina Krause, René St-Arnaud, Alice Arabian, Andreas Radbruch, Susanne Hartmann, Margitta Worm, Guido Heine
The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29109120/cd27-mediated-regulatory-t-cell-depletion-and-effector-t-cell-costimulation-both-contribute-to-antitumor-efficacy
#18
Anna Wasiuk, James Testa, Jeff Weidlick, Crystal Sisson, Laura Vitale, Jenifer Widger, Andrea Crocker, Lawrence J Thomas, Joel Goldstein, Henry C Marsh, Tibor Keler, Li-Zhen He
CD27, a member of the TNFR superfamily, is constitutively expressed in most T cells and plays crucial roles in T cell effector functions. The costimulation and antitumor activity of CD27 agonistic Abs have been well documented in mouse models. Clinical testing of a human IgG1 anti-CD27 Ab, varlilumab (clone 1F5), is ongoing in cancer patients. In this study, we set out to further understand CD27 as an immunomodulatory target and to address the mechanism of antitumor efficacy using different IgG isotypes of 1F5 in human CD27-transgenic mice...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29107141/immunoadjuvant-activity-in-mice-of-polysaccharides-isolated-from-the-leaves-of-panax-ginseng-c-a-meyer
#19
Su-Hyun Hwang, Myoung-Sook Shin, Taek Joon Yoon, Kwang-Soon Shin
Our previous study showed polysaccharide (GS-P) isolated from the leaves of Panax ginseng C.A. Meyer possessed anti-tumor metastatic activity in mouse model. In this study, we evaluated the immunoadjuvant effect of GS-P on the induction of humoral and cellular immune responses against ovalbumin (OVA) in mice. When mice were immunized subcutaneously with OVA admixed with or without GS-P, the OVA+GS-P group showed significantly higher antibody production than the group immunized with OVA alone. This suggests that GS-P has the ability to enhance the adaptive immune response...
October 26, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29103968/anti-pd-l1-tgf%C3%AE-r2-m7824-fusion-protein-induces-immunogenic-modulation-of-human-urothelial-carcinoma-cell-lines-rendering-them-more-susceptible-to-immune-mediated-recognition-and-lysis
#20
Italia Grenga, Renee N Donahue, Morgan L Gargulak, Lauren M Lepone, Mario Roselli, Marijo Bilusic, Jeffrey Schlom
BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis...
November 2, 2017: Urologic Oncology
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