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Antigen affinity

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https://www.readbyqxmd.com/read/29158832/clinical-translation-and-first-in-human-use-of-44-sc-sc-psma-617-for-pet-imaging-of-metastasized-castrate-resistant-prostate-cancer
#1
Elisabeth Eppard, Ana de la Fuente, Martina Benešová, Ambreen Khawar, Ralph A Bundschuh, Florian C Gärtner, Barbara Kreppel, Klaus Kopka, Markus Essler, Frank Rösch
BACKGROUND: Various trivalent radiometals are well suited for labeling of DOTA-conjugated variants of Glu-ureido-based prostate-specific membrane antigen (PSMA) inhibitors. The DOTA-conjugate PSMA-617 has proven high potential in PSMA radioligand therapy (PSMA-RLT) of prostate cancer as well as PET imaging when labeled with lutetium-177 and gallium-68 respectively. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for pre-therapeutic dosimetry or intraoperative applications...
2017: Theranostics
https://www.readbyqxmd.com/read/29157448/ab-initio-conformational-epitope-structure-prediction-using-genetic-algorithm-and-svm-for-vaccine-design
#2
Basem Ameen Moghram, Emad Nabil, Amr Badr
BACKGROUND AND OBJECTIVE: T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i...
January 2018: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/29156405/effective-immobilization-of-au-nanoparticles-on-tio2-loaded-graphene-for-a-novel-sandwich-type-immunosensor
#3
Ying Chen, Yu Li, Dongmei Deng, Haibo He, Xiaoxia Yan, Zhenxin Wang, Chunhai Fan, Liqiang Luo
A novel and sensitive sandwich immunosensor for amperometric determination of carcinoembryonic antigen (CEA) was designed using Au nanoparticles-titanium dioxide-graphene (AuNPs-TiO2-graphene) nanocomposites. Dopamine-functionalized graphene was firstly prepared by π-stacking interaction, and TiO2 was then attached to the surface of dopamine-graphene by the specificity and high affinity of enediol ligands to Ti (IV). Afterwards, AuNPs-TiO2-graphene nanocomposites were synthesized with photo-reduction approach under ultraviolet irradiation...
November 17, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29150937/cgmp-production-and-analysis-of-bg505-sosip-664-an-extensively-glycosylated-trimeric-hiv-1-envelope-glycoprotein-vaccine-candidate
#4
Antu K Dey, Albert Cupo, Gabriel Ozorowski, Vaneet K Sharma, Anna-Janina Behrens, Eden P Go, Thomas J Ketas, Anila Yasmeen, Per J Klasse, Eddy Sayeed, Heather Desaire, Max Crispin, Ian A Wilson, Rogier W Sanders, Thomas Hassell, Andrew Ward, John P Moore
We describe the properties of BG505 SOSIP.664 HIV-1 envelope glycoprotein trimers produced under current Good Manufacturing Practice (cGMP) conditions. These proteins are the first of a new generation of native-like trimers that are the basis for many structure-guided immunogen development programs aimed at devising how to induce broadly neutralizing antibodies (bNAbs) to HIV-1 by vaccination. The successful translation of this prototype demonstrates the feasibility of producing similar immunogens on an appropriate scale and of an acceptable quality for Phase I experimental medicine clinical trials...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150443/kinetic-mechanism-of-controlled-fab-arm-exchange-for-the-formation-of-bispecific-immunoglobulin-g1-antibodies
#5
Dennis R Goulet, Steven J Orcutt, Adam Zwolak, Theo Rispens, Aran Labrijn, Rob N de Jong, William M Atkins, Mark L Chiu
Bispecific antibodies (bsAbs) combine the antigen specificities of two distinct Abs and demonstrate therapeutic promise based on novel mechanisms of action. Among the many platforms for creating bsAbs, controlled Fab-arm exchange (cFAE) has proven useful based on minimal changes to native Ab structure and the simplicity with which bsAbs can be formed from two parental Abs. Despite a published protocol for cFAE and its widespread use in the pharmaceutical industry, the reaction mechanism has not been determined...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29149704/gold-nanoparticles-as-an-adjuvant-influence-of-size-shape-and-technique-of-combination-with-cpg-on-antibody-production
#6
Lev A Dykman, Sergey A Staroverov, Alexander S Fomin, Vitaly A Khanadeev, Boris N Khlebtsov, Vladimir A Bogatyrev
Gold nanoparticles (GNPs) are advantageous as an adjuvant in the design of effective vaccines and in the preparation of high-affinity antibodies to haptens and complete antigens. Another method of activating immunocompetent cells with colloidal gold is to conjugate GNPs with CpG oligodeoxynucleotides (ODNs). We examined how the size and shape of GNPs and various combinations of GNPs and CpG ODNs 1826 affect the immune response. When animals were injected with a model antigen (BSA) coupled to gold nanospheres (diameters, 15 and 50nm), nanorods, nanoshells, and nanostars, the titers of the resultant antibodies differed substantially...
November 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#7
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29140786/selection-of-an-anticalin%C3%A2-against-the-membrane-form-of-hsp70-via-bacterial-surface-display-and-its-theranostic-application-in-tumour-models
#8
Lars Friedrich, Petra Kornberger, Claudia T Mendler, Gabriele Multhoff, Markus Schwaiger, Arne Skerra
We describe the selection of Anticalins against a common tumour surface antigen, human Hsp70, using functional display on live E. coli cells as fusion with a truncated EspP autotransporter. While found intracellularly in normal cells, Hsp70 is frequently exposed in a membrane-bound state on the surface of tumour cells and, even more pronounced, in metastases or after radiochemotherapy. Employing a recombinant Hsp70 fragment comprising residues 383-548 as target, Anticalins were selected from a naive bacterial library...
November 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29139018/vaccination-against-hydatidosis-molecular-cloning-and-optimal-expression-of-the-eg95nc-recombinant-antigen-in-escherichia-coli
#9
M Jazouli, M Lightowlers, C G Gauci, K Tadlaoui, A Belmlih, M M Ennaji, M Elharrak
Cystic echinococcosis (CE) is a widely distributed zoonosis that is highly endemic in the Mediterranean basin. The disease represents a serious public health threat and causes economic losses. The parasite life-cycle involves dogs and ruminants as definitive and intermediate hosts; humans are accidently infected, causing serious clinical issues. Vaccination of ruminants and dog treatments represent the most efficient measures to prevent parasite transmission. The recombinant protein vaccine, EG95, has been used successfully in sheep vaccine trials against CE in several countries...
November 14, 2017: Protein Journal
https://www.readbyqxmd.com/read/29138425/timescale-separation-of-positive-and-negative-signaling-creates-history-dependent-responses-to-ige-receptor-stimulation
#10
Brooke Harmon, Lily A Chylek, Yanli Liu, Eshan D Mitra, Avanika Mahajan, Edwin A Saada, Benjamin R Schudel, David A Holowka, Barbara A Baird, Bridget S Wilson, William S Hlavacek, Anup K Singh
The high-affinity receptor for IgE expressed on the surface of mast cells and basophils interacts with antigens, via bound IgE antibody, and triggers secretion of inflammatory mediators that contribute to allergic reactions. To understand how past inputs (memory) influence future inflammatory responses in mast cells, a microfluidic device was used to precisely control exposure of cells to alternating stimulatory and non-stimulatory inputs. We determined that the response to subsequent stimulation depends on the interval of signaling quiescence...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132366/prokaryotic-expression-and-characterization-of-the-heterodimeric-construction-of-znt8-and-its-application-for-autoantibodies-detection-in-diabetes-mellitus
#11
Natalia I Faccinetti, Luciano L Guerra, Adriana V Sabljic, Silvina S Bombicino, Bruno D Rovitto, Ruben F Iacono, Edgardo Poskus, Aldana Trabucchi, Silvina N Valdez
BACKGROUND: In the present work we described the recombinant production and characterization of heterodimeric construction ZnT8-Arg-Trp325 fused to thioredoxin using a high-performance expression system such as Escherichia coli. In addition, we apply this novel recombinant antigen in a non-radiometric method, with high sensitivity, low operational complexity and lower costs. RESULTS: ZnT8 was expressed in E. coli as a fusion protein with thioredoxin (TrxZnT8). After 3 h for induction, recombinant protein was obtained from the intracellular soluble fraction and from inclusion bodies and purified by affinity chromatography...
November 13, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/29132144/a-neoantigen-fitness-model-predicts-tumour-response-to-checkpoint-blockade-immunotherapy
#12
Marta Łuksza, Nadeem Riaz, Vladimir Makarov, Vinod P Balachandran, Matthew D Hellmann, Alexander Solovyov, Naiyer A Rizvi, Taha Merghoub, Arnold J Levine, Timothy A Chan, Jedd D Wolchok, Benjamin D Greenbaum
Checkpoint blockade immunotherapies enable the host immune system to recognize and destroy tumour cells. Their clinical activity has been correlated with activated T-cell recognition of neoantigens, which are tumour-specific, mutated peptides presented on the surface of cancer cells. Here we present a fitness model for tumours based on immune interactions of neoantigens that predicts response to immunotherapy. Two main factors determine neoantigen fitness: the likelihood of neoantigen presentation by the major histocompatibility complex (MHC) and subsequent recognition by T cells...
November 8, 2017: Nature
https://www.readbyqxmd.com/read/29131585/antibody-templated-assembly-of-an-rna-mimic-of-green-fluorescent-protein
#13
Alessandro Bertucci, Alessandro Porchetta, Francesco Ricci
One of the most intriguing ways through which Nature achieves regulation of biological pathways encompasses the coordination of non-covalent interactions that bring biomolecules to be co-localized in a designated restricted space. This nano-confinement leads to a drastic increase in the effective local concentration of the species involved, which ultimately triggers reactions that would otherwise not occur at the low concentrations found in cells. Inspired by this mechanism, we have explored the possibility of using antibodies as bivalent biomolecular substrates for the templated assembly of a functional RNA structure...
November 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29129076/comprehensive-molecular-characterization-of-a-cisplatin-specific-monoclonal-antibody
#14
Lena Ruhe, Stefanie Ickert, Ulrike Hochkirch, Johanna Hofmann, Sebastian Beck, Jürgen Thomale, Michael W Linscheid
Despite their immense and rapidly increasing importance as analytical tools or therapeutic drugs, the detailed structural features of particular monoclonal antibodies are widely unknown. Here, an antibody already in use for diagnostic purposes and for molecular dosimetry studies in cancer therapy with very high affinity and specificity for cisplatin-induced DNA modifications was studied extensively. The molecular structure and modifications as well as the antigen specificity were investigated mainly by mass spectrometry...
November 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29128519/genetic-structure-of-two-erythrocyte-binding-antigens-of-plasmodium-falciparum-reveals-a-contrasting-pattern-of-selection
#15
Pramita Chowdhury, Srikanta Sen, Sumana Datta Kanjilal, Sanghamitra Sengupta
Erythrocyte binding antigens 175 (EBA-175) and 140 (EBA-140) play key roles in erythrocyte invasion by binding to glycophorin A (GPA) and C (GPC) respectively in human malaria. Since antigenic variation in malaria endemic region is a major barrier to development of effective vaccine, we explore the nature and pattern of sequence diversity of these two vaccine candidates in Kolkata, India. Population genetic parameters based on parasite sequences representing region II of Pfeba-175 and Pfeba-140 genes were estimated using DnaSP V...
November 8, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29128091/non-protease-native-allergens-partially-purified-from-bodies-of-eight-domestic-mites-using-p-aminobenzamidine-ligand
#16
T Erban, R Klubal
BACKGROUND: Optimised purification steps for concentrating trace target native antigens are needed. Combining the p-aminobenzamidine ligand with protease inactivation enables partial purification of mite non-protease allergens lacking proteases. OBJECTIVE: We sought to analyse in detail proteins obtained using this method from eight species of synanthropic acaridid mites and tested IgE reactivity using pooled human sera. MATERIALS AND METHODS: Proteins affinity bound to p-aminobenzamidine as a ligand were identified by MALDI TOF/TOF...
November 8, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29127283/environmental-sensing-by-mature-b-cells-is-controlled-by-the-transcription-factors-pu-1-and-spib
#17
Simon N Willis, Julie Tellier, Yang Liao, Stephanie Trezise, Amanda Light, Kristy O'Donnell, Lee Ann Garrett-Sinha, Wei Shi, David M Tarlinton, Stephen L Nutt
Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands, and microbial products. Ets family transcription factors regulate many aspects of haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29125719/safety-pharmacokinetics-and-immunogenicity-of-obiltoxaximab-after-intramuscular-administration-to-healthy-humans
#18
Christa F Nagy, Timothy S Leach, Alex King, Robert Guttendorf
Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high-affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29123516/avidity-and-bystander-suppressive-capacity-of-human-regulatory-t-cells-expressing-de-novo-autoreactive-t-cell-receptors-in-type-1-diabetes
#19
Wen-I Yeh, Howard R Seay, Brittney Newby, Amanda L Posgai, Filipa Botelho Moniz, Aaron Michels, Clayton E Mathews, Jeffrey A Bluestone, Todd M Brusko
The ability to alter antigen specificity by T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene transfer has facilitated personalized cellular immune therapies in cancer. Inversely, this approach can be harnessed in autoimmune settings to attenuate inflammation by redirecting the specificity of regulatory T cells (Tregs). Herein, we demonstrate efficient protocols for lentiviral gene transfer of TCRs that recognize type 1 diabetes-related autoantigens with the goal of tissue-targeted induction of antigen-specific tolerance to halt β-cell destruction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29118259/matrix-binding-checkpoint-immunotherapies-enhance-antitumor-efficacy-and-reduce-adverse-events
#20
Jun Ishihara, Kazuto Fukunaga, Ako Ishihara, Hans M Larsson, Lambert Potin, Peyman Hosseinchi, Gabriele Galliverti, Melody A Swartz, Jeffrey A Hubbell
Immune checkpoint blockade exhibits considerable antitumor activity, but previous studies have reported instances of severe treatment-related adverse events. We sought to explore local immune checkpoint blockade, with an antibody (Ab) form that would be retained intra- or peritumorally, limiting systemic exposure. To accomplish this, we conjugated the checkpoint blockade Abs to an extracellular matrix (ECM)-super-affinity peptide derived from placenta growth factor-2 (PlGF-2123-144). We show enhanced tissue retention and lower Ab concentrations in blood plasma after PlGF-2123-144 conjugation, reducing systemic side effects such as the risk of autoimmune diabetes...
November 8, 2017: Science Translational Medicine
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