keyword
MENU ▼
Read by QxMD icon Read
search

TCR

keyword
https://www.readbyqxmd.com/read/28645940/t-cell-receptors-for-clinical-therapy-in-vitro-assessment-of-toxicity-risk
#1
Andre Kunert, Matthias Obenaus, Cor Hj Lamers, Thomas Blankenstein, Reno Debets
Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645373/strategies-and-methods-of-transcription-coupled-repair-studies-in-vitro-and-in-vivo
#2
Vitaly Epshtein, Venu Kamarthapu, Evgeny Nudler
Transcription-coupled repair (TCR) serves an important role in preserving genome integrity and maintaining fidelity of replication. Coupling transcription to DNA repair requires a coordinated action of several factors, including transcribing RNA polymerase and various transcription modulators and repair proteins. To study TCR in molecular detail, it is important to employ defined protein complexes in vitro and defined genetic backgrounds in vivo. In this chapter, we present methods to interrogate various aspects of TCR at different stages of repair...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28642802/perk-dependent-defective-tcr-mediated-activation-of-cd4-t-cells-in-end-stage-renal-disease-patients
#3
Ling Huang, Nicolle H R Litjens, Nynke M Kannegieter, Mariska Klepper, Carla C Baan, Michiel G H Betjes
BACKGROUND: Patients with end-stage renal disease (ESRD) have an impaired immune response with a prematurely aged T-cell system. Mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) and p38, regulate diverse cellular programs by transferring extracellular signals into an intracellular response. T cell receptor (TCR)-induced phosphorylation of ERK (pERK) may show an age-associated decline, which can be reversed by inhibiting dual specific phosphatase (DUSP) 6, a cytoplasmic phosphatase with substrate specificity to dephosphorylate pERK...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28642246/modulation-of-endoplasmic-reticulum-stress-controls-cd4-t-cell-activation-and-anti-tumor-function
#4
Jessica E Thaxton, Caroline Wallace, Brian Riesenberg, Yongliang Zhang, Chrystal Paulos, Craig Beeson, Bei Liu, Zihai Li
The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca(2+) stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca(2+) buffering protein. We hypothesized that the ER stress response may be important for CD4(+) T-cell activation and that gp96 may be integral to this process...
June 22, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#5
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28638937/anti-gitr-antibody-treatment-increases-tcr-repertoire-diversity-of-regulatory-but-not-effector-t-cells-engaged-in-the-immune-response-against-b16-melanoma
#6
Bozena Scirka, Edyta Szurek, Maciej Pietrzak, Grzegorz Rempala, Pawel Kisielow, Leszek Ignatowicz, Arkadiusz Miazek
Crosslinking of glucocorticoid-induced TNF family-related receptor (GITR) with agonist antibodies restores cancer immunity by enhancing effector T cell (Teff) responses while interfering with intra-tumor regulatory T cell (Treg) stability and/or accumulation. However, how anti-GITR antibody infusion changes T cell receptor (TCR) repertoire of Teffs and Tregs engaged in anti-tumor immune response is unclear. Here, we used a transgenic mouse model (TCRmini) where T cells express naturally generated but limited TCR repertoire to trace the fate of individual T cells recognizing B16 melanoma in tumor-bearing mice, treated or non-treated with an anti-GITR monoclonal antibody DTA-1...
June 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28638741/innate-%C3%AE-%C3%AE-t17-cells-play-a-protective-role-in-dss-induced-colitis-via-recruitment-of-gr-1-cd11b-myeloid-suppressor-cells
#7
Xuan Sun, Yihua Cai, Chris Fleming, Zan Tong, Zhenglong Wang, Chuanlin Ding, Minye Qu, Huang-Ge Zhang, Jian Suo, Jun Yan
Innate γδ T cells play critical roles in mucosal immunity such as regulating intestinal epithelial homeostasis. In addition, γδ T cells are significantly increased in the inflamed mucosa of patients with ulcerative colitis. However, γδ T cells are a heterogeneous population. IL-17-producing versus IFNγ-producing γδ T cells play differential roles in different disease settings. Therefore, dissecting the exact role of different subsets of γδ T cells in colitis is essential for understanding colitis immunopathogenesis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638739/ewing-sarcoma-partial-regression-without-gvhd-by-chondromodulin-i-hla-a-02-01-specific-allorestricted-t-cell-receptor-transgenic-t-cells
#8
Uwe Thiel, Sebastian J Schober, Ingo Einspieler, Andreas Kirschner, Melanie Thiede, David Schirmer, Katja Gall, Franziska Blaeschke, Oxana Schmidt, Susanne Jabar, Andreas Ranft, Rebeca Alba Rubío, Uta Dirksen, Thomas G P Grunewald, Poul H Sorensen, Günther H S Richter, Irene Teichert von Lüttichau, Dirk H Busch, Stefan E G Burdach
Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1-specific allorestricted T cell receptor (TCR) wild-type and transgenic cytotoxic (CD8(+)) T cells against ES. Patients and Methods: Three refractory HLA-A2(+) ES patients were treated with HLA-A*02:01/peptide-specific allorepertoire-derived (i.e., allorestricted) CD8(+) T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637901/caveolin-1-influences-lfa-1-redistribution-upon-tcr-stimulation-in-cd8-t-cells
#9
Jessica G Borger, Vicky L Morrison, Andrew Filby, Celine Garcia, Liisa M Uotila, Fabio Simbari, Susanna C Fagerholm, Rose Zamoyska
TCR stimulation by peptide-MHC complexes on APCs requires precise reorganization of molecules into the area of cellular contact to form an immunological synapse from where T cell signaling is initiated. Caveolin (Cav)1, a widely expressed transmembrane protein, is involved in the regulation of membrane composition, cellular polarity and trafficking, and the organization of signal transduction pathways. The presence of Cav1 protein in T cells was identified only recently, and its function in this context is not well understood...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28637900/activation-of-mouse-tcrb-uncoupling-runx1-function-from-its-cooperative-binding-with-ets1
#10
Jiang-Yang Zhao, Oleg Osipovich, Olivia I Koues, Kinjal Majumder, Eugene M Oltz
T lineage commitment requires the coordination of key transcription factors (TFs) in multipotent progenitors that transition them away from other lineages and cement T cell identity. Two important TFs for the multipotent progenitors to T lineage transition are RUNX1 and ETS1, which bind cooperatively to composite sites throughout the genome, especially in regulatory elements for genes involved in T lymphopoiesis. Activation of the TCR β (Tcrb) locus in committed thymocytes is a critical process for continued development of these cells, and is mediated by an enhancer, Eβ, which harbors two RUNX-ETS composite sites...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28637663/ny-eso-1-tcr-single-edited-central-memory-and-memory-stem-t-cells-to-treat-multiple-myeloma-without-inducing-gvhd
#11
Sara Mastaglio, Pietro Genovese, Zulma Magnani, Eliana Ruggiero, Elisa Landoni, Barbara Camisa, Giulia Schiroli, Elena Provasi, Angelo Lombardo, Andreas Reik, Nicoletta Cieri, Martina Rocchi, Giacomo Oliveira, Giulia Escobar, Monica Casucci, Bernhard Gentner, Antonello Spinelli, Anna Mondino, Attilio Bondanza, Luca Vago, Maurilio Ponzoni, Fabio Ciceri, Michael C Holmes, Luigi Naldini, Chiara Bonini
Transfer of T cell receptors (TCR) specific for tumor-associated antigens is a promising approach for cancer immunotherapy. We developed the TCR gene editing technology, that is based on the knockout of the endogenous TCR α and β genes, followed by the introduction of tumor-specific TCR genes, and that proved safer and more effective than conventional TCR gene transfer. While successful, complete editing requires extensive cell manipulation and four transduction procedures. Here we propose a novel and clinically feasible 'single TCR editing' (SE) approach, based on the disruption of the endogenous TCR α chain only, followed by the transfer of genes encoding for a tumor specific TCR...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28636592/quantifiable-predictive-features-define-epitope-specific-t-cell-receptor-repertoires
#12
Pradyot Dash, Andrew J Fiore-Gartland, Tomer Hertz, George C Wang, Shalini Sharma, Aisha Souquette, Jeremy Chase Crawford, E Bridie Clemens, Thi H O Nguyen, Katherine Kedzierska, Nicole L La Gruta, Philip Bradley, Paul G Thomas
T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 10(15) (ref. 1) to as high as 10(61) (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#13
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28635957/itk-signalling-via-the-ras-irf4-pathway-regulates-the-development-and-function-of-tr1-cells
#14
Weishan Huang, Sabrina Solouki, Nicholas Koylass, Song-Guo Zheng, Avery August
Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635677/t-cell-manipulation-strategies-to-prevent-graft-versus-host-disease-in-haploidentical-stem-cell-transplantation
#15
REVIEW
Jayakumar Vadakekolathu, Sergio Rutella
Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably high rates of graft rejection and graft-versus-host disease (GVHD)...
June 21, 2017: Biomedicines
https://www.readbyqxmd.com/read/28634816/critical-biological-parameters-modulate-affinity-as-a-determinant-of-function-in-t-cell-receptor-gene-modified-t-cells
#16
Timothy T Spear, Yuan Wang, Kendra C Foley, David C Murray, Gina M Scurti, Patricia E Simms, Elizabeth Garrett-Mayer, Lance M Hellman, Brian M Baker, Michael I Nishimura
T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28634215/vaccination-with-high-affinity-epitopes-impairs-antitumor-efficacy-by-increasing-pd-1expression-on-cd8-t-cells
#17
Christopher D Zahm, Viswa Colluru, Douglas G McNeel
Antitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination...
June 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#18
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28630305/multiple-layers-of-heterogeneity-and-subset-diversity-in-human-mait-cell-responses-to-distinct-microorganisms-and-to-innate-cytokines
#19
Joana Dias, Edwin Leeansyah, Johan K Sandberg
Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the limited known diversity of riboflavin metabolite antigens have suggested that MAIT cells are relatively homogeneous and uniform in responses against diverse microbes carrying the riboflavin biosynthesis pathway...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630092/characterization-of-high-avidity-cytomegalovirus-specific-t-cells-with-differential-tetramer-binding-coappearing-after-allogeneic-stem-cell-transplantation
#20
Justyna Ogonek, Kriti Verma, Christian Schultze-Florey, Pavankumar Varanasi, Susanne Luther, Patrick Schweier, Wolfgang Kühnau, Gudrun Göhring, Elke Dammann, Michael Stadler, Arnold Ganser, Ulrike Koehl, Christian Koenecke, Eva M Weissinger, Lothar Hambach
CMV reactivation is a major complication after allogeneic stem cell transplantation (SCT). Immune reconstitution of CMV-specific CTLs (CMV-CTLs) is essential for virus control. During CMV-CTL monitoring using mutated HLA/CMV tetramers selectively detecting high-avidity T cells, we observed coappearance of CMV-CTLs with low (CMV tet(low) CTLs) and high tetramer binding (CMV tet(high) CTLs) in 53/115 CMV IgG(+) patients stem cell transplanted from CMV IgG(+) donors. However, the relevance of these coappearing differentially tetramer binding ("dual") CMV-CTLs was unclear...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
keyword
keyword
19049
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"