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Antigen affinity

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https://www.readbyqxmd.com/read/29339550/relative-target-affinities-of-t-cell-dependent-bispecific-antibodies-determine-biodistribution-in-a-solid-tumor-mouse-model
#1
Danielle Mandikian, Nene Takahashi, Amy A Lo, Ji Li, Jeffrey Eastham-Anderson, Dionysos Slaga, Jason Ho, Maria Hristopoulos, Robyn Clark, Klara Totpal, Kedan Lin, Sean B Joseph, Mark S Dennis, Saileta Prabhu, Teemu T Junttila, C Andrew Boswell
Anti-HER2/CD3, a T cell-dependent bispecific antibody (TDB) construct, induces T cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic synapse. TDB design is a very challenging process that requires consideration of multiple parameters. While therapeutic antibody design strategy is commonly driven by striving for the highest attainable antigen binding affinity, little is known about how the affinity of each TDB arm can affect the targeting ability of the other arm and the consequent distribution and efficacy...
January 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29339495/streamlined-circular-proximity-ligation-assay-provides-high-stringency-and-compatibility-with-low-affinity-antibodies
#2
Roxana Jalili, Joe Horecka, James R Swartz, Ronald W Davis, Henrik H J Persson
Proximity ligation assay (PLA) is a powerful tool for quantitative detection of protein biomarkers in biological fluids and tissues. Here, we present the circular proximity ligation assay (c-PLA), a highly specific protein detection method that outperforms traditional PLA in stringency, ease of use, and compatibility with low-affinity reagents. In c-PLA, two proximity probes bind to an analyte, providing a scaffolding that positions two free oligonucleotides such that they can be ligated into a circular DNA molecule...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339376/tumor-immunity-and-survival-as-a-function-of-alternative-neopeptides-in-human-cancer
#3
Andrew J Rech, David Balli, Alejandro Mantero, Hemant Ishwaran, Katherine L Nathanson, Ben Z Stanger, Robert H Vonderheide
The immune system exerts antitumor activity via T cell-dependent recognition of tumor-specific antigens. Although the number of tumor neopeptides - peptides derived from somatic mutations - often correlates with immune activity and survival, most classically defined high-affinity neopeptides (CDNs) are not immunogenic, and only rare CDNs have been linked to tumor rejection. Thus, the rules of tumor antigen recognition remain incompletely understood. Here, we analyzed neopeptides, immune activity, and clinical outcome from 6,324 patients across 27 tumor types...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29335534/cell-type-specific-potent-wnt-signaling-blockade-by-bispecific-antibody
#4
Nam-Kyung Lee, Yafeng Zhang, Yang Su, Scott Bidlingmaier, Daniel W Sherbenou, Kevin D Ha, Bin Liu
Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29333938/structure-based-engineering-to-restore-high-affinity-binding-of-an-isoform-selective-anti-tgf%C3%AE-1-antibody
#5
Dana M Lord, Julie J Bird, Denise M Honey, Annie Best, Anna Park, Ronnie R Wei, Huawei Qiu
Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering...
January 15, 2018: MAbs
https://www.readbyqxmd.com/read/29324815/biophysical-insights-from-a-single-chain-camelid-antibody-directed-against-the-disrupted-in-schizophrenia-1-protein
#6
Antony S K Yerabham, Andreas Müller-Schiffmann, Tamar Ziehm, Andreas Stadler, Sabrina Köber, Xela Indurkhya, Rita Marreiros, Svenja V Trossbach, Nicholas J Bradshaw, Ingrid Prikulis, Dieter Willbold, Oliver H Weiergräber, Carsten Korth
Accumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate important protein-protein interactions and to harbor functionally important phosphorylation sites and disease-associated polymorphisms. However, long disordered regions and oligomer-forming subdomains have so far impeded structural analysis. VHH domains derived from camelid heavy chain only antibodies are minimal antigen binding modules with appreciable solubility and stability, which makes them well suited for the stabilizing proteins prior to structural investigation...
2018: PloS One
https://www.readbyqxmd.com/read/29322650/molecular-characterization-of-the-%C3%AE-amyloid-4-10-epitope-of-plaque-specific-a%C3%AE-antibodies-by-affinity-mass-spectrometry-using-alanine-site-mutation
#7
Raluca Ștefănescu, Loredana Lupu, Marilena Manea, Roxana E Iacob, Michael Przybylski
Alzheimer disease is a neurodegenerative disease affecting an increasing number of patients worldwide. Current therapeutic strategies are directed to molecules capable to block the aggregation of the β-amyloid(1-42) (Aβ) peptide and its shorter naturally occurring peptide fragments into toxic oligomers and amyloid fibrils. Aβ-specific antibodies have been recently developed as powerful antiaggregation tools. The identification and functional characterization of the epitope structures of Aβ antibodies contributes to the elucidation of their mechanism of action in the human organism...
January 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29320333/prostate-specific-membrane-antigen-pet-clinical-utility-in-prostate-cancer-normal-patterns-pearls-and-pitfalls
#8
Michael S Hofman, Rodney J Hicks, Tobias Maurer, Matthias Eiber
Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 (68Ga)-PSMA-11 (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR) imaging...
January 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29317506/the-interplay-between-citrullination-and-hla-drb1-polymorphism-in-shaping-peptide-binding-hierarchies-in-rheumatoid-arthritis
#9
Yi Tian Ting, Jan Petersen, Sri H Ramarathinam, Stephen W Scally, Khai L Loh, Ranjeny Thomas, Anish Suri, Daniel G Baker, Anthony W Purcell, Hugh H Reid, Jamie Rossjohn
The HLA-DRB1 locus is strongly associated with rheumatoid arthritis (RA) susceptibility, whereupon citrullinated self-peptides bind to HLA-DR molecules bearing the shared epitope (SE) amino acid motif.  However, the differing propensity for citrullinated/non-citrullinated self-peptides to bind given HLA-DR allomorphs remains unclear.  Here, we used a fluorescence polarisation assay to determine a hierarchy of binding affinities of 34 self-peptides implicated in RA against three HLA-DRB1 allomorphs (HLA-DRB1*04:01/*04:04/*04:05) each possessing the SE motif...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29315598/improved-methods-for-predicting-peptide-binding-affinity-to-mhc-class-ii-molecules
#10
Kamilla Kjaergaard Jensen, Massimo Andreatta, Paolo Marcatili, Søren Buus, Jason A Greenbaum, Zhen Yan, Alessandro Sette, Bjoern Peters, Morten Nielsen
Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC class II peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan...
January 6, 2018: Immunology
https://www.readbyqxmd.com/read/29315388/galectin-3-and-cancer-stemness
#11
Pratima Nangia-Makker, Victor Hogan, Avraham Raz
Over the last few decades galectin-3, a carbohydrate binding protein, with affinity for N-acetyllactosamine residues, has been unique due to the regulatory roles it performs in processes associated with tumor progression and metastasis such as cell proliferation, homotypic/ heterotypic aggregation, dynamic cellular transformation, migration and invasion, survival and apoptosis. Structure-function association of galectin-3 reveals that it consists of a short amino terminal motif, which regulates its nuclear-cytoplasmic shuttling; a collagen α-like domain, susceptible to cleavage by matrix metalloproteases and prostate specific antigen (PSA); accountable for its oligomerization and lattice formation, and a carbohydrate recognition/binding domain containing the anti-death motif of the Bcl2 protein family...
January 5, 2018: Glycobiology
https://www.readbyqxmd.com/read/29312858/de-novo-glomerular-diseases-after-renal-transplantation-how-is-it-different-from-recurrent-glomerular-diseases
#12
REVIEW
Fedaey Abbas, Mohsen El Kossi, Jon Kim Jin, Ajay Sharma, Ahmed Halawa
The glomerular diseases after renal transplantation can occur de novo, i.e., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original disease in the native kidney. There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease. However, structural alterations in transplanted kidney add to dilemma in diagnosis. These changes in architecture of histopathology can happen due to: (1) exposure to the immunosuppression specifically the calcineurin inhibitors (CNI); (2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cell-mediated immunological onslaught; (3) post-transplant viral infections; (4) ischemia-reperfusion injury; and (5) hyperfiltration injury...
December 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/29306443/bacterial-surface-glycans-microarray-and-qcm-strategies-for-glycophenotyping-and-exploration-of-recognition-by-host-receptors
#13
Ioanna Kalograiaki, María A Campanero-Rhodes, Davide Proverbio, Begoña Euba, Junkal Garmendia, Teodor Aastrup, Dolores Solís
Bacterial surfaces are decorated with a diversity of carbohydrate structures that play important roles in the bacteria-host relationships. They may offer protection against host defense mechanisms, elicit strong antigenic responses, or serve as ligands for host receptors, including lectins of the innate immune system. Binding by these lectins may trigger defense responses or, alternatively, promote attachment, thereby enhancing infection. The outcome will depend on the particular bacterial surface landscape, which may substantially differ among species and strains...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29301020/discovery-of-internalizing-antibodies-to-basal-breast-cancer-cells
#14
Yu Zhou, Hao Zou, Christina Yau, Lequn Zhao, Steven C Hall, Daryl C Drummond, Shauna Farr-Jones, John W Park, Christopher C Benz, James D Marks
We present a strategy to discover recombinant monoclonal antibodies (mAbs) to specific cancers and demonstrate this approach using basal subtype breast cancers. A phage antibody library was depleted of antibodies to common cell surface molecules by incubation with luminal breast cancer cell lines, and then selected on a single basal-like breast cancer cell line (MDA-MB-231) for binding associated receptor-mediated endocytosis. Additional profiling against two luminal and four basal-like cell lines revealed 61 unique basal-specific mAbs from a pool of 1440 phage antibodies...
December 28, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29298343/epcam-peptide-primed-dendritic-cell-vaccination-confers-significant-anti-tumor-immunity-in-hepatocellular-carcinoma-cells
#15
Yoo Jin Choi, Seong-Joon Park, You-Soo Park, Hee Sung Park, Kwang Mo Yang, Kyu Heo
Cancer stem-like cells (CSCs) may play a key role in tumor initiation, self-renewal, differentiation, and resistance to current treatments. Dendritic cells (DCs) play a vital role in host immune reactions as well as antigen presentation. In this study, we explored the suitability of using CSC peptides as antigen sources for DC vaccination against human breast cancer and hepatocellular carcinoma (HCC) with the aim of achieving CSC targeting and enhancing anti-tumor immunity. CD44 is used as a CSC marker for breast cancer and EpCAM is used as a CSC marker for HCC...
2018: PloS One
https://www.readbyqxmd.com/read/29296261/novel-recombinant-traceable-c-met-antagonist-avimer-antibody-mimetic-obtained-by-bacterial-expression-analysis
#16
Bahram Baghban Kohnehrouz, Afsaneh Talischian, Alireza Dehnad, Shahnoush Nayeri
Background: Avimers are originally types of artificial proteins with multiple binding sites for specific binding to certain antigens. Various radioisotopes and nanoparticles link these molecules, which are widely used in early detection in tissue imaging, treatment and study on carcinogenesis. Among these, c-Met antagonist avimer (C426 avimer), with ability to bind the c-Met receptor of tyrosine kinase (RTK) is an attractive candidate for targeted cancer therapy. In this study, a novel traceable C426 avimer gene was designed and introduced by adding the 12nt tracer binding site encoded four specific amino acid residues at the C-terminal region of C426 avimer coding sequence...
January 2018: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/29295582/theoretical-and-experimental-comparison-of-different-formats-of-immunochromatographic-serodiagnostics
#17
Dmitriy V Sotnikov, Anatoly V Zherdev, Boris B Dzantiev
In this study, a comparative theoretical and experimental analysis of two immuno-chromatographic serodiagnostics schemes, which differ in the immobilization of immunoreagents and the order of the formation of immune complexes, is performed. Based on the theoretical models, the assays are characterized to determine which scheme has a higher quantity of the detected complex and thus ensures the sensitivity of the analysis. The results show that for the effective detection of low-affinity antibodies, the scheme involving the immobilization of the antigen on gold nanoparticles and the antibody-binding protein on the test strip was more sensitive than the predominantly used scheme, which inverts the immunoreagents' locations...
December 25, 2017: Sensors
https://www.readbyqxmd.com/read/29290804/an-albumin-binding-polypeptide-both-targets-cytotoxic-t-lymphocyte-vaccines-to-lymph-nodes-and-boosts-vaccine-presentation-by-dendritic-cells
#18
Peng Wang, Peng Zhao, Shuyun Dong, Tiefeng Xu, Xiao He, Mingnan Chen
Rationale: Albumin-binding carriers have been shown to target cytotoxic T lymphocyte (CTL) vaccines to lymph nodes (LNs) and improve the efficacy of the vaccines. However, it was not clear whether the improved efficacy is solely due to the LN targeting, which prompted this study. Methods: First, we generated a fusion protein consisting of an albumin-binding domain (ABD) and an immune-tolerant elastin-like polypeptide (iTEP). Then, we examined the binding between this fusion protein, termed ABD-iTEP, and mouse serum albumin (MSA)...
2018: Theranostics
https://www.readbyqxmd.com/read/29290115/lipidated-brartemicin-analogues-are-potent-th1-stimulating-vaccine-adjuvants
#19
Amy J Foster, Masahiro Nagata, Xiuyuan Lu, Amy T Lynch, Zakaria Omahdi, Eri Ishikawa, Sho Yamasaki, Mattie S M Timmer, Bridget L Stocker
Effective Th1-stimulating vaccine adjuvants often engage the innate immune system via the activation of antigen presenting cells (APCs). Macrophage inducible C-type lectin (Mincle) is an activating pattern recognition receptor (PRR) expressed on the cell surface of APCs and has been identified as a potential target for Th1-stimulating adjuvants. In particular, trehalose dibehenate (TDB) is a leading Mincle-agonist and has shown much promise as an adjuvant. Herein, we report on the synthesis and adjuvanticity of rationally designed brartemicin analogues containing short, medium, and long chain lipids...
December 30, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29289300/novel-near-infrared-spectrum-analysis-tool-synergy-adaptive-moving-window-model-based-on-immune-clone-algorithm
#20
Shenghao Wang, Yuyan Zhang, Fuyi Cao, Zhenying Pei, Xuewei Gao, Xu Zhang, Yong Zhao
This paper presents a novel spectrum analysis tool named synergy adaptive moving window modeling based on immune clone algorithm (SA-MWM-ICA) considering the tedious and inconvenient labor involved in the selection of pre-processing methods and spectral variables by prior experience. In this work, immune clone algorithm is first introduced into the spectrum analysis field as a new optimization strategy, covering the shortage of the relative traditional methods. Based on the working principle of the human immune system, the performance of the quantitative model is regarded as antigen, and a special vector corresponding to the above mentioned antigen is regarded as antibody...
February 13, 2018: Analytica Chimica Acta
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