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T cell affinity

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https://www.readbyqxmd.com/read/29239915/preclinical-assessment-of-car-t-cell-therapy-targeting-the-tumor-antigen-5t4-in-ovarian-cancer
#1
Gemma L Owens, Victoria E Sheard, Milena Kalaitsidou, Daniel Blount, Yatish Lad, Eleanor J Cheadle, Richard J Edmondson, Gurdeep Kooner, David E Gilham, Richard Harrop
Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome both quantitative and qualitative shortfalls of the host immune system relating to the detection and subsequent destruction of tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step in the ability to utilize CAR T cells for the treatment of cancer. The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer...
December 12, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29236469/synthetic-phenolic-antioxidants-cause-perturbation-in-steroidogenesis-in-vitro-and-in-vivo
#2
Xiaoxi Yang, Wenting Song, Na Liu, Zhendong Sun, Ruirui Liu, Qian S Liu, Qunfang Zhou, Guibin Jiang
Synthetic phenolic antioxidants (SPAs) are closely correlated with human life due to their extensive usages, and increasing concerns have been raised on their biosafety. The previous controversial findings caused continuous debates on their potential endocrine disrupting effects. In the present study, four commonly used SPAs, including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butyl hydroquinone (TBHQ) and 2,2'-methylenebis(6-tert-butyl-4-methylphenol) (AO2246), were investigated for their estrogenic effects, and the results from in vitro screening assays showed SPAs themselves had negligible estrogen receptor binding affinities...
December 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29236306/rs4705342-polymorphism-is-involved-in-the-tumorigenesis-of-hbv-positive-hcc-by-altering-the-binding-affinity-of-hbv-induced-nf-kb-with-the-promoter-region-of-microrna-143
#3
Yin Xiuli, Sun Shiying, Zhao Junyan, Yang Jing, Lei Xiaofei, Xu Changqing, Li Kun
BACKGROUND: The objective of this study was to explore the role of rs4705342 located in the miR-143 promoter in relation to the control of HBV positive HCC and the underlying molecular mechanism. METHOD: A luciferase assay was performed to explore the factors which influenced miR-143 transcription activity and the target gene of miR-143. This would further be confirmed by ChIP assay. Western-blot and real-time PCR were performed to identify the relationship between miR-143 and ORP8...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29234980/low-dose-interleukin-2-as-a-modulator-of-treg-homeostasis-after-hsct-current-understanding-and-future-perspectives
#4
REVIEW
Ken-Ichi Matsuoka
CD4+CD25+Foxp3+ Treg is a functionally distinct subset of mature T cells with broad suppressive activity and has been shown to play an important role in the establishment of immune tolerance after HSCT. Altered cytokine environment in post-HSCT lymphopenia with a relative functional deficiency of IL-2 could hamper the reconstitution of Treg, leading to refractory GVHD. Based on the theory of low-dose IL-2 in which Treg can be selectively stimulated through the high-affinity IL-2 receptor, clinical studies have been conducted and demonstrated that low-dose IL-2 administration can restore Treg homeostasis and promote the expansion of this subset on the polymorphic processes of Treg reconstitution after HSCT...
December 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29232769/antiparkinsonian-and-antidyskinetic-profiles-of-two-novel-potent-and-selective-nociceptin-orphanin-fq-receptor-agonists
#5
Ludovico Arcuri, Salvatore Novello, Martina Frassineti, Daniela Mercatelli, Clarissa Anna Pisanò, Ilaria Morella, Stefania Fasano, Blair V Journigan, Michael E Meyer, Willma E Polgar, Riccardo Brambilla, Nurulain T Zaveri, Michele Morari
BACKGROUND AND PURPOSE: We previously showed that Nociceptin/orphanin FQ opioid peptide (NOP) receptor agonists attenuate the expression of levodopa-induced dyskinesia in animal models of Parkinson's disease. We now investigate the efficacy of two novel, potent and chemically distinct NOP receptor agonists, AT-390 and AT-403, to improve parkinsonian disabilities and attenuate dyskinesia development and expression. EXPERIMENTAL APPROACH: Binding affinity and functional efficacy of AT-390 and AT-403 at the opioid receptors were determined in radioligand displacement assays and in GTPγS binding assay respectively, conducted in Chinese hamster ovary cells...
December 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29230151/integrating-a-19f-mri-tracer-agent-into-the-clinical-scale-manufacturing-of-a-t-cell-immunotherapy
#6
Charles F O'Hanlon, Tamara Fedczyna, Shannon Eaker, William D Shingleton, Brooke M Helfer
Leukocyte immunotherapies have made great progress in the treatment of cancer. Recent reports on the treatment of B-cell malignancies using Chimeric Antigen Receptor and affinity enhanced T-Cell Receptor therapies have demonstrated encouraging clinical results. As investigators begin to explore the treatment of solid tumors with these cells, the hurdle of evaluating T-cell homing to and persistence at the site of disease remain. Significant challenges regarding the GMP manufacture and administration of a therapeutic dose of millions to billions of transduced T-cells remain...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29229779/subtle-changes-at-the-variable-domain-interface-of-the-t-cell-receptor-can-strongly-increase-affinity
#7
Preeti Sharma, David M Kranz
Most affinity maturation campaigns for antibodies and T cell receptors (TCRs) operate on the residues at the binding site, located within the loops known as complementarity determining regions (CDRs). Accordingly, mutations in contact residues or so-called second shell residues that increase affinity are typically identified by directed evolution using combinatorial libraries. Here we used single codon libraries of both CDR and non-CDR residues to generate a deep mutational scan of a human TCR against the cancer antigen MART-1/HLA-A2...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29228015/development-of-an-iron-selective-antioxidant-probe-with-protective-effects-on-neuronal-function
#8
Olimpo García-Beltrán, Natalia P Mena, Pabla Aguirre, Germán Barriga-González, Antonio Galdámez, Edgar Nagles, Tatiana Adasme, Cecilia Hidalgo, Marco T Núñez
Iron accumulation, oxidative stress and calcium signaling dysregulation are common pathognomonic signs of several neurodegenerative diseases, including Parkinson´s and Alzheimer's diseases, Friedreich ataxia and Huntington's disease. Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable. Here, we report the synthesis and characterization of N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetamide, named CT51, which exhibited potent free radical neutralizing activity both in vitro and in cells...
2017: PloS One
https://www.readbyqxmd.com/read/29227213/productive-common-light-chain-libraries-yield-diverse-panels-of-high-affinity-bispecific-antibodies
#9
Thomas Van Blarcom, Kevin Lindquist, Zea Melton, Wai Ling Cheung, Chris Wagstrom, Dan McDonough, Cendy Valle Oseguera, Sheng Ding, Andrea Rossi, Shobha Potluri, Purnima Sundar, Steven Pitts, Marina Sirota, Meri Galindo Casas, Yu Yan, Jeffrey Jones, Zygy Roe-Zurz, Surabhi Srivatsa Srinivasan, Wenwu Zhai, Jaume Pons, Arvind Rajpal, Javier Chaparro-Riggers
The commercial success of bispecific antibodies generally has been hindered by the complexities associated with generating appropriate molecules for both research scale and large scale manufacturing purposes. Bispecific IgG (BsIgG) based on two antibodies that use an identical common light chain can be combined with a minimal set of Fc mutations to drive heavy chain heterodimerization in order to address these challenges. However, the facile generation of common light chain antibodies with properties similar to traditional monoclonal antibodies has not been demonstrated and they have only been used sparingly...
December 11, 2017: MAbs
https://www.readbyqxmd.com/read/29226612/glutaraldehyde-cross-linking-increases-the-stability-of-lumbricus-terrestris-erythrocruorin
#10
Athul Rajesh, Devon Zimmerman, Kyle Spivack, Osheiza Abdulmalik, Jacob Elmer
Since donated red blood cells must be constantly refrigerated, they are not available in remote areas and battlefields. We have previously shown that the hemoglobin of the earthworm Lumbricus terrestris (LtEc) is an effective and safe substitute for donated blood that is stable enough to be stored for long periods at the relatively high temperatures that may be encountered in remote areas. The goal of this study was to increase the thermal stability of LtEc by covalently cross-linking LtEc with glutaraldehyde (gLtEc)...
December 11, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/29225464/apolipoprotein-e3-mediated-cellular-uptake-of-reconstituted-high-density-lipoprotein-bearing-core-3-10-or-17-nm-hydrophobic-gold-nanoparticles
#11
Skylar T Chuang, Young-Seok Shon, Vasanthy Narayanaswami
We have developed a high-density lipoprotein (HDL)-based platform for transport and delivery of hydrophobic gold nanoparticles (AuNPs). The ability of apolipoprotein E3 (apoE3) to act as a high-affinity ligand for the low-density lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNPs into glioblastoma cells. AuNPs of 3, 10, and 17 nm diameter, the latter two synthesized by phase transfer process, were solubilized by integration with phospholipids and apoE3, yielding reconstituted HDL (rHDL) bearing AuNPs...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29225429/in-silico-validation-of-d7-salivary-protein-derived-b-and-t-cell-epitopes-of-aedes-aegypti-as-potential-vaccine-to-prevent-transmission-of-flaviviruses-and-togaviruses-to-humans
#12
Sathish Sankar, Mageshbabu Ramamurthy, Balaji Nandagopal, Gopalan Sridharan
Mosquito (Aedes aegyptii) salivary proteins play a crucial role in facilitating viral transmission from vector-to-host due to their role in facilitating the "blood meal" of the vector. Three main proteins, D7, aegyptin and Sialokinin play a role in this process. Using in-silico programs, we identified B- and T-cell epitopes in the mosquito salivary proteins D7 long and short form. T-cell epitopes with high affinity to the most prevalent HLA MHC class-I supertypes among different population groups was chosen...
2017: Bioinformation
https://www.readbyqxmd.com/read/29224741/identification-of-d-seco-modified-steroid-derivatives-with-affinity-for-estrogen-receptor-%C3%AE-and-%C3%AE-isoforms-using-a-non-transcriptional-fluorescent-cell-assay-in-yeast
#13
Sofija S Bekić, Maja A Marinović, Edward T Petri, Marija N Sakač, Andrea R Nikolić, Vesna V Kojić, Andjelka S Ćelić
Synthesis and biological evaluation of steroidal derivatives with anticancer properties is an active area of drug discovery. Here we measured the relative affinities of D-seco modified steroidal derivatives for estrogen receptor α, estrogen receptor β or androgen receptor ligand binding domains using an optimized non-transcriptional fluorescent cell assay in yeast. Ligand binding domains of steroid receptors were expressed in-frame with yellow fluorescent protein in the yeast Sacharomyces cerevisiae. Addition of known steroid ligands to yeast expressing the appropriate cognate receptor results in increased fluorescence intensity, enabling estimation of receptor binding affinities in a dose-response and time-dependent manner...
December 7, 2017: Steroids
https://www.readbyqxmd.com/read/29223138/plant-expressed-fc-fusion-protein-tetravalent-dengue-vaccine-with-inherent-adjuvant-properties
#14
Mi Young Kim, Alastair Copland, Kaustuv Nayak, Anmol Chandele, Muhammad Shamsher Ahmed, Qibo Zhang, Gil Reynolds Diogo, Matthew John Paul, Sven Hofmann, Moon-Sik Yang, Yong-Suk Jang, Julian K-C Ma, Rajko Reljic
Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi-Pasteur Denvaxia vaccine does not protect children under the age of nine and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant-expression to produce a humanised and highly immunogenic Poly-Immunoglobulin G Scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralising antibodies and evidence of cell-mediated immunity...
December 9, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29221580/mechanisms-of-allergen-immunotherapy-for-inhaled-allergens-and-predictive-biomarkers
#15
REVIEW
Mohamed H Shamji, Stephen R Durham
Allergen immunotherapy is effective in patients with IgE-dependent allergic rhinitis and asthma. When immunotherapy is given continuously for 3 years, there is persistent clinical benefit for several years after its discontinuation. This disease-modifying effect is both antigen-specific and antigen-driven. Clinical improvement is accompanied by decreases in numbers of effector cells in target organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid cells. Immunotherapy results in the production of blocking IgG/IgG4 antibodies that can inhibit IgE-dependent activation mediated through both high-affinity IgE receptors (FcεRI) on mast cells and basophils and low-affinity IgE receptors (FcεRII) on B cells...
December 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#16
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29217732/peptide-blocking-of-pd-1-pd-l1-interaction-for-cancer-immunotherapy
#17
Chunlin Li, Nengpan Zhang, Jundong Zhou, Chen Ding, Yaqing Jin, Xueyuan Cui, Kefeng Pu, Yimin Zhu
Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. Monoclonal antibody (mAb) targeting to PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung cancer or merkel cell carcinoma by the Food and Drug Administration (FDA). However, the high cost of the antibody can limit its application. In our study, TPP-1 (targeting PD-L1 peptide), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods...
December 7, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29217201/expression-and-purification-of-the-human-epidermal-growth-factor-receptor-extracellular-domain
#18
Linpeng Wang, Jing Yan, Jingyun Yan, Huanhuan Xu, Dengyang Zhang, Xuanjun Wang, Jun Sheng
In the fields of drug discovery and protein science, small quantities of proteins are always needed to investigate or validate protein-protein (or protein-small molecule) interactions. Traditional transient or stable expression method to obtain recombinant proteins in eukaryotic systems can be laborious and time-consuming, especially when multiple protein variants are required. Here, we present a fast and convenient method for obtaining small quantities of recombinant human epidermal growth factor receptor (rhEGFR) ectodomain protein, which could be efficiently extended to the expression of other eukaryotic proteins...
December 4, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/29217157/functional-histamine-h3-and-adenosine-a2a-receptor-heteromers-in-recombinant-cells-and-rat-striatum
#19
Ricardo Márquez-Gómez, Meridith T Robins, Citlaly Gutiérrez-Rodelo, Juan-Manuel Arias, Jesús-Alberto Olivares-Reyes, Richard M van Rijn, José-Antonio Arias-Montaño
In the striatum, histamine H3 receptors (H3Rs) are co-expressed with adenosine A2A receptors (A2ARs) in the cortico-striatal glutamatergic afferents and the GABAergic medium-sized spiny neurons that originate from the indirect pathway of the basal ganglia. This location allows H3Rs and A2ARs to regulate the striatal GABAergic and glutamatergic transmission. However, whether these receptors can physically interact has not yet been assessed. To test this hypothesis, a heteromer-selective in vitro assay was used to detect functional complementation between a chimeric A2AR302-Gαqi4 and wild-type H3Rs in transfected HEK-293 cells...
December 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29216561/design-synthesis-and-evaluation-of-an-anthraquinone-derivative-conjugated-to-myelin-basic-protein-immunodominant-mbp85-99-epitope-towards-selective-immunosuppression
#20
Anthi Tapeinou, Efstathia Giannopoulou, Carmen Simal, Bjarke E Hansen, Haralabos Kalofonos, Vasso Apostolopoulos, Alexios Vlamis-Gardikas, Theodore Tselios
Anthraquinone type compounds, especially di-substituted amino alkylamino anthraquinones have been widely studied as immunosuppressants. The anthraquinone ring is part of mitoxandrone that has been used for the treatment of multiple sclerosis (MS) and several types of tumors. A desired approach for the treatment of MS would be the immunosuppression and elimination of specific T cells that are responsible for the induction of the disease. Herein, the development of a peptide compound bearing an anthraquinone derivative with the potential to specifically destroy the encephalitogenic T cells responsible for the onset of MS is described...
November 24, 2017: European Journal of Medicinal Chemistry
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