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https://www.readbyqxmd.com/read/29157295/single-cell-multiplexed-cytokine-profiling-of-cd19-car-t-cells-reveals-a-diverse-landscape-of-polyfunctional-antigen-specific-response
#1
Qiong Xue, Emily Bettini, Patrick Paczkowski, Colin Ng, Alaina Kaiser, Timothy McConnell, Olja Kodrasi, Máire F Quigley, James Heath, Rong Fan, Sean Mackay, Mark E Dudley, Sadik H Kassim, Jing Zhou
BACKGROUND: It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. METHODS: We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29156741/screening-epitopes-on-systemic-lupus-erythematosus-autoantigens-with-a-peptide-array
#2
Lin Wang, Chenjun Hao, Yongqiu Deng, Yanbo Liu, Shiliang Hu, Yangang Peng, Manna He, Jinhu Fu, Ming Liu, Jia Chen, Xiaoming Chen
Systemic lupus erythematosus (SLE) is a common autoimmune disease. Many autoantibodies are closely associated with SLE. However, the specific epitopes recognized and bound by these autoantibodies are still unclear. This study screened the binding epitopes of SLE-related autoantibodies using a high-throughput screening method. Epitope prediction on 12 SLE-related autoantigens was performed using the Immune Epitope Database and Analysis Resource (IEDB) software. The predicted epitopes were synthesized into peptides and developed into a peptide array...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154976/microneedle-arrays-coated-with-charge-reversal-ph-sensitive-copolymers-improve-antigen-presenting-cells-homing-dna-vaccine-delivery-and-immune-responses
#3
Huu Thuy Trang Duong, Nak Won Kim, Thavasyappan Thambi, V H Giang Phan, Min Sang Lee, Yue Yin, Ji Hoon Jeong, Doo Sung Lee
Successful delivery of a DNA vaccine to antigen-presenting cells and their subsequent stimulation of CD4(+) and CD8(+) T cell immunity remains an inefficient process. In general, the delivery of prophylactic vaccines is mainly mired by low transfection efficacy, poor immunogenicity, and safety issues from the materials employed. Currently, several strategies have been exploited to improve immunogenicity, but an effective strategy for safe and pain-free delivery of DNA vaccines is complicated. Herein, we report the rapid delivery of polyplex-based DNA vaccines using microneedle arrays coated with a polyelectrolyte multilayer assembly of charge reversal pH-responsive copolymer and heparin...
November 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29147604/tap1-down-regulation-elicits-immune-escape-and-poor-prognosis-in-colorectal-cancer
#4
Agnes Ling, Anna Löfgren-Burström, Pär Larsson, Xingru Li, Maria L Wikberg, Åke Öberg, Roger Stenling, Sofia Edin, Richard Palmqvist
The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29141850/autoantibodies-against-hsf1-and-ccdc155-as-biomarkers-of-early-stage-high-grade-serous-ovarian-cancer
#5
Amy L Wilson, Laura R Moffitt, Nadine Duffield, Adam Rainczuk, Tom W Jobling, Magdalena Plebanski, Andrew N Stephens
BACKGROUND: Tumor-directed circulating autoantibodies (AAbs) are a well-established feature of many solid tumor types, and are often observed prior to clinical disease manifestation. As such, they may provide a good indicator of early disease development. We have conducted a pilot study to identify novel AAbs as markers of early stage HGSOCs. METHODS: A rare cohort of patients with early (FIGO stage Ia-c) HGSOCs for IgG, IgA and IgM-mediated AAb reactivity using high content protein arrays (containing 9184 individual proteins)...
November 15, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29133290/cd137-4-1bb-costimulation-modifies-dna-methylation-in-cd8-t-cell-relevant-genes
#6
M Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Carmen Molina, Saray Garasa, Arantza Azpilicueta, Inaki Etxeberria, Alfonso R Sanchez-Paulete, Alan J Korman, Manel Esteller, Juan Sandoval, Ignacio Melero
CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA-methylation arrays were carried out on human peripheral blood CD8+ T lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials for cancer immunotherapy. Several genes showed consistent methylation patterns in response to CD137 costimulation, which were confirmed by pyrosequencing in a series of healthy donors...
November 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29128714/multiplex-immunoassays-using-virus-tethered-gold-microspheres-by-dc-impedance-based-flow-cytometry
#7
Jihun Rho, Woohyuk Jang, Inseong Hwang, Dahye Lee, Chang Heon Lee, Taek Dong Chung
Bead-based multiplex immunoassays for common use require enhanced sensitivity and effective prevention of non-specific adsorption, as well as miniaturization of the detection device. In this work, we have implemented virus-tethered gold microspheres for multiplex immunoassay applications, employing a DC impedance-based flow cytometer as a detection element. The advantages of virus-tethered gold microspheres, including excellent prevention of non-specific adsorption, are extended to signal enhancement arising from the large quantity of antibody loading on each virion, and to flexible movement of filamentous virus...
November 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29126472/a-novel-visible-light-driven-photoelectrochemical-immunosensor-based-on-multi-amplification-strategy-for-ultrasensitive-detection-of-microcystin-lr
#8
Jie Wei, Aori Qileng, Yun Yan, Hongtao Lei, Shengsen Zhang, Weipeng Liu, Yingju Liu
An ultrasensitive photoelectrochemical (PEC) immunoassay based on multiple signal amplification strategy was fabricated for the detection of microcystin-LR (MC-LR). The CdS/TiO2 nanorod arrays (CdS/TiO2 NRAs) modified FTO electrode, which can weaken the self-oxidation by photogenerated holes of CdS nanoparticles, and limit the recombination of electron-hole pairs and broaden optical absorption of TiO2 NRAs, was used as a visible-light driven material to immobilize antigens. Then, Fe3O4 nanoparticles/polydopamine (Fe3O4@PDA) was used as the carrier to load secondary antibody (Ab2) and horseradish peroxidase (HRP), where Fe3O4 nanoparticles and HRP can synergistically accelerate the oxidation of 4-chloro-1-naphthol (4-CN) by H2O2 to produce biocatalytic precipitation (BCP) on the surface of modified electrode...
November 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29123514/assessment-of-the-combined-effect-of-epstein-barr-virus-and-plasmodium-falciparum-infections-on-endemic-burkitt-lymphoma-using-a-multiplex-serological-approach
#9
Ruth Aguilar, Delphine Casabonne, Cristina O'Callaghan-Gordo, Marta Vidal, Joseph J Campo, Nora Mutalima, Evelina Angov, Sheetij Dutta, Deepak Gaur, Chetan E Chitnis, Virander Chauhan, Angelika Michel, Silvia de Sanjosé, Tim Waterboer, Manolis Kogevinas, Rob Newton, Carlota Dobaño
Epstein-Barr virus (EBV) is a necessary cause of endemic Burkitt lymphoma (eBL), while the role of Plasmodium falciparum in eBL remains uncertain. This study aimed to generate new hypotheses on the interplay between both infections in the development of eBL by investigating the IgG and IgM profiles against several EBV and P. falciparum antigens. Serum samples collected in a childhood study in Malawi (2005-2006) from 442 HIV-seronegative children (271 eBL cases and 171 controls) between 1.4 and 15 years old were tested by quantitative suspension array technology against a newly developed multiplex panel combining 4 EBV antigens [Z Epstein-Barr replication activator protein (ZEBRA), early antigen-diffuse component (EA-D), EBV nuclear antigen 1, and viral capsid antigen p18 subunit (VCA-p18)] and 15 P...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29116516/screening-phage-display-antibody-libraries-using-protein-arrays
#10
Ricardo Jara-Acevedo, Paula Díez, María González-González, Rosa María Dégano, Nieves Ibarrola, Rafael Góngora, Alberto Orfao, Manuel Fuentes
Phage-display technology constitutes a powerful tool for the generation of specific antibodies against a predefined antigen. The main advantages of phage-display technology in comparison to conventional hybridoma-based techniques are: (1) rapid generation time and (2) antibody selection against an unlimited number of molecules (biological or not). However, the main bottleneck with phage-display technology is the validation strategies employed to confirm the greatest number of antibody fragments. The development of new high-throughput (HT) techniques has helped overcome this great limitation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29112174/mirnas-melanoma-and-microenvironment-an-intricate-network
#11
REVIEW
Gabriele Romano, Lawrence N Kwong
miRNAs are central players in cancer biology and they play a pivotal role in mediating the network communication between tumor cells and their microenvironment. In melanoma, miRNAs can impair or facilitate a wide array of processes, and here we will focus on: the epithelial to mesenchymal transition (EMT), the immune milieu, and metabolism. Multiple miRNAs can affect the EMT process, even at a distance, for example through exosome-mediated mechanisms. miRNAs also strongly act on some components of the immune system, regulating the activity of key elements such as antigen presenting cells, and can facilitate an immune evasive/suppressive phenotype...
November 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29109798/multiplexed-nucleic-acid-programmable-protein-arrays
#12
Xiaobo Yu, Lusheng Song, Brianne Petritis, Xiaofang Bian, Haoyu Wang, Jennifer Viloria, Jin Park, Hoang Bui, Han Li, Jie Wang, Lei Liu, Liuhui Yang, Hu Duan, David N McMurray, Jacqueline M Achkar, Mitch Magee, Ji Qiu, Joshua LaBaer
Rationale: Cell-free protein microarrays display naturally-folded proteins based on just-in-time in situ synthesis, and have made important contributions to basic and translational research. However, the risk of spot-to-spot cross-talk from protein diffusion during expression has limited the feature density of these arrays. Methods: In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot...
2017: Theranostics
https://www.readbyqxmd.com/read/29109092/screening-for-multiple-autoantibodies-in-plasma-of-patients-with-breast-cancer
#13
REVIEW
Lauren Bassaro, Stephen J Russell, Elzbieta Pastwa, Stella A Somiari, Richard I Somiari
BACKGROUND/AIM: Autoantibodies have potential as circulating biomarkers for early cancer detection. This study aimed to screen for known autoantibodies in human plasma using an Autoantibody Profiling System (APS) and quantify the levels in plasma of donors with/without breast cancer. MATERIALS AND METHODS: Plasma from nine female donors diagnosed with breast cancer (test group) and nine matched donors with no personal history of cancer (reference group) were screened with an APS containing probes for 30 autoantibodies...
November 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29109028/enhancing-immunogenicity-of-antigens-through-sustained-intradermal-delivery-using-chitosan-microneedles-with-a-patch-dissolvable-design
#14
Mei-Chin Chen, Kuan-Ying Lai, Ming-Hung Ling, Chun-Wei Lin
Reducing the dosage required for vaccination is highly desirable, particularly in cases of epidemic emergencies. This study evaluated the potential of a chitosan microneedle (MN) system with a patch-dissolvable design for low-dose immunization. This system comprises antigen-loaded chitosan MNs and a hydrophilic polyvinyl alcohol/polyvinyl pyrrolidone supporting array patch, which provides extra strength to achieve complete MN insertion and then quickly dissolves in the skin to reduce patch-induced skin irritation...
November 3, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29100671/-nettling-the-host-breaking-of-tolerance-in-chronic-inflammation-and-chronic-infection
#15
REVIEW
Sladjana Skopelja-Gardner, Jonathan D Jones, William F C Rigby
How and why we break tolerance to self-proteins still remains a largely unanswered question. Neutrophils have been identified as a rich source of autoantigens in a wide array of autoimmune diseases that arise as a consequence of different environmental and genetic factors, e.g. rheumatoid arthritis (RA), lupus, vasculitis, cystic fibrosis (CF) etc. Specifically, neutrophil extracellular trap (NET) formation has been identified as a link between innate and adaptive immune responses in autoimmunity. Autoantigens including neutrophil granular proteins (targeted by anti-neutrophil cytoplasmic antibodies, ANCA) as well as post-translationally modified proteins, i...
October 31, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29097674/functionalized-vertical-gan-micro-pillar-arrays-with-high-signal-to-background-ratio-for-detection-and-analysis-of-proteins-secreted-from-breast-tumor-cells
#16
Mun-Ki Choi, Gil-Sung Kim, Jin-Tak Jeong, Jung-Taek Lim, Won-Yong Lee, Ahmad Umar, Sang-Kwon Lee
The detection of cancer biomarkers has recently attracted significant attention as a means of determining the correct course of treatment with targeted therapeutics. However, because the concentration of these biomarkers in blood is usually relatively low, highly sensitive biosensors for fluorescence imaging and precise detection are needed. In this study, we have successfully developed vertical GaN micropillar (MP) based biosensors for fluorescence sensing and quantitative measurement of CA15-3 antigens. The highly ordered vertical GaN MP arrays result in the successful immobilization of CA15-3 antigens on each feature of the arrays, thereby allowing the detection of an individual fluorescence signal from the top surface of the arrays owing to the high regularity of fluorophore-tagged MP spots and relatively low background signal...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29094051/improved-scfv-anti-lox-1-binding-activity-by-fusion-with-lox-1-binding-peptides
#17
Wei Hu, Qiuhong Xie, Hongyu Xiang
The oxidized low-density lipoprotein receptor-1 (LOX-1) targeted single-chain variable fragment (scFvs) is a promising molecule for the targeted delivery of imaging and therapeutic molecules of atherosclerotic diseases; however, its applications are limited by the inherent low antigen affinity. In this study, the three-dimensional (3D) model of the anti-LOX-1 scFv was constructed and its docking with the LOX-1 protein was developed. To improve the LOX-1-binding activity, the anti-LOX-1 scFv was designed to fuse with one of three LOX-1-binding heptapeptides, LTPATAI, FQTPPQL, and LSIPPKA, at its N-terminus and C-terminus and in the linker region, which have different LOX-1-binding interfaces with the anti-LOX-1 scFv analyzed by an array of computational approaches...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29083070/breastfeeding-and-autoimmunity-programing-health-from-the-beginning
#18
REVIEW
Vânia Vieira Borba, Kassem Sharif, Yehuda Shoenfeld
Breast milk is not only a completely adapted nutrition source for the newborn but also an impressive array of immune-active molecules that afford protection against infections and shape mucosal immune responses. Decisive imprinting events might be modulated during the first months of life with potential health long-term effects, enhancing the importance of breastfeeding as a major influence on the immune system correct development and modifying disease susceptibility. The aim of this review was to clarify the link between breastfeeding and autoimmune diseases, inquiring the related mechanisms, based on data available in the literature...
October 30, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29072486/multiplexing-determination-of-cancer-associated-biomarkers-by-surface-enhanced-raman-scattering-using-ordered-gold-nanohoneycomb-arrays
#19
Li Li, Chang Liu, Xiaowei Cao, Lianqiao Tan, Wenbo Lu
AIM: Here, a multiplex surface-enhanced Raman scattering (SERS) based assay for simultaneous quantitation of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) was developed. METHODS: SERS tags of nanostars and SERS substrates of nanobowl arrays were functionalized with labeling and capturing antibodies, respectively. In presence of antigens, SERS tags, antigens and SERS substrates formed sandwich structure. RESULTS: The SERS-based technique showed a wide linear range from 0...
October 26, 2017: Bioanalysis
https://www.readbyqxmd.com/read/29068555/diagnostic-utility-of-cortactin-antibodies-in-myasthenia-gravis
#20
REVIEW
Isabel Illa, Elena Cortés-Vicente, María Ángeles Martínez, Eduard Gallardo
Patients with myasthenia gravis (MG) without antibodies to the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) have been classified as having double-seronegative myasthenia gravis (dSNMG). We used the sera from six dSNMG patients with positive immunohistochemistry assays in a protein array to screen reactivity with 9000 human proteins. We identified cortactin, an intracellular protein that interacts with agrin/MuSK favoring AChR aggregation, as a new antigen in dSNMG. We then designed an in-house enzyme-linked immunosorbent assay as a screening assay and confirmed these results by western blot...
October 25, 2017: Annals of the New York Academy of Sciences
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