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https://www.readbyqxmd.com/read/28635517/a-primer-for-oncoimmunology-immunooncology
#1
Brad Bolon, Famke Aeffner
Oncoimmunology (or immunooncology) is a burgeoning specialty of precision ("personalized") medicine designed to heighten the antitumor response of the immune system against molecules expressed excessively or only by tumor cells. This focus is necessary, as cancers are polyclonal tissues comprised of antigenically heterogeneous cells, the exact composition of which is shaped by the balance between antitumor immunity and tumor-promoting inflammation. Key targets include enhancing immune system (especially T cell) reactivity, inhibiting immune checkpoints, and promoting tumor cytolysis...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28634215/vaccination-with-high-affinity-epitopes-impairs-antitumor-efficacy-by-increasing-pd-1expression-on-cd8-t-cells
#2
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/28633193/trictide-a-tricellulin-derived-peptide-to-overcome-cellular-barriers
#3
Jimmi Cording, Basak Arslan, Christian Staat, Sophie Dithmer, Susanne M Krug, Anneliese Krüger, Philipp Berndt, Ramona Günther, Lars Winkler, Ingolf E Blasig, Reiner F Haseloff
The majority of tight junction (TJ) proteins restrict the paracellular permeation of solutes via their extracellular loops (ECLs). Tricellulin tightens tricellular TJs (tTJs) and regulates bicellular TJ (bTJ) proteins. We demonstrate that the addition of recombinantly produced extracellular loop 2 (ECL2) of tricellulin opens cellular barriers. The peptidomimetic trictide, a synthetic peptide derived from tricellulin ECL2, increases the passage of ions, as well as of small and larger molecules up to 10 kDa, between 16 and 30 h after application to human epithelial colorectal adenocarcinoma cell line 2...
June 20, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28630091/b-1a-cells-protect-mice-from-sepsis-critical-role-of-creb
#4
Monowar Aziz, Nichol E Holodick, Thomas L Rothstein, Ping Wang
Bacterial sepsis is a serious life-threatening condition caused by an excessive immune response to infection. B-1 cells differ from conventional B-2 cells by their distinct phenotype and function. A subset of B-1 cells expressing CD5, known as B-1a cells, exhibits innate immune activity. Here we report that B-1a cells play a beneficial role in sepsis by mitigating exaggerated inflammation through a novel mechanism. Using a mouse model of bacterial sepsis, we found that the numbers of B-1a cells in various anatomical locations were significantly decreased...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28630062/the-transcription-factor-nfat1-participates-in-the-induction-of-cd4-t-cell-functional-exhaustion-during-plasmodium-yoelii-infection
#5
Rachel Y Ames, Li-Min Ting, Inessa Gendlina, Kami Kim, Fernando Macian
Repeated stimulation of T cells that occurs in the context of chronic infection results in progressively reduced responsiveness of T cells to pathogen-derived antigens. This phenotype, known as T cell exhaustion, occurs during chronic infections caused by a variety of pathogens, from persistent viruses to parasites. Unlike the memory cells that typically form after successful pathogen clearance following an acute infection, exhausted T cells secrete lower levels of effector cytokines, proliferate less in response to cognate antigen, and up-regulate cell-surface inhibitory molecules such as PD-1 and LAG-3...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28628043/immunotherapy-for-transplantation-associated-viral-infections
#6
Claire Roddie, Karl S Peggs
Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections following allogeneic hematopoietic stem cell transplantation (HSCT) are a major cause of morbidity and mortality. Early clinical trials demonstrate that adoptive transfer of donor-derived virus-specific T cells to restore virus-specific immunity is an effective strategy to control CMV and EBV infection after HSCT, conferring protection in 70%-90% of patients. The field has evolved rapidly to develop solutions to some of the manufacturing challenges identified in early clinical studies, such as prolonged in vitro culture, optimization of the purity of the virus-specific T cell product, the potential limitations of targeting a single viral antigen, and how to manage the patient with a virus-naive donor...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627740/biofabrication-of-soft-tissue-templates-for-engineering-the-bone-ligament-interface
#7
Ella Harris, Yurong Liu, Grainne Cuniffe, David Morrissey, Simon Carroll, Kevin Mulhall, Daniel J Kelly
Regenerating damaged tissue interfaces remains a significant clinical challenge, requiring recapitulation of the structure, composition and function of the native enthesis. In the ligament-to-bone interface this region transitions from ligament to fibrocartilage, to calcified cartilage and then to bone. This gradation in tissue types facilitates the transfer of load between soft and hard structures while minimizing stress concentrations at the interface. Previous attempts to engineer the ligament-bone interface have utilized various scaffold materials with an array of various cell types and/or biological cues...
June 19, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28620386/the-rise-of-allogeneic-natural-killer-cells-as-a-platform-for-cancer-immunotherapy-recent-innovations-and-future-developments
#8
REVIEW
John P Veluchamy, Nina Kok, Hans J van der Vliet, Henk M W Verheul, Tanja D de Gruijl, Jan Spanholtz
Natural killer (NK) cells are critical immune effector cells in the fight against cancer. As NK cells in cancer patients are highly dysfunctional and reduced in number, adoptive transfer of large numbers of cytolytic NK cells and their potential to induce relevant antitumor responses are widely explored in cancer immunotherapy. Early studies from autologous NK cells have failed to demonstrate significant clinical benefit. In this review, the clinical benefits of adoptively transferred allogeneic NK cells in a transplant and non-transplant setting are compared and discussed in the context of relevant NK cell platforms that are being developed and optimized by various biotech industries with a special focus on augmenting NK cell functions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28617989/1-25-dihydroxyvitamin-d3-induced-dendritic-cells-suppress-experimental-autoimmune-encephalomyelitis-by-increasing-proportions-of-the-regulatory-lymphocytes-and-reducing-th1-th17-cells
#9
Zhongxiang Xie, Jingtao Chen, Chao Zheng, Jing Wu, Yun Cheng, Shan Zhu, Chenhong Lin, Qingqing Cao, Jie Zhu, Tao Jin
Dendritic cells (DCs), a bridge of innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in the autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) and adoptive transferred the tolerogenic DCs (VD3-DCs) into EAE mice...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28615225/enhanced-therapeutic-efficacy-and-memory-of-tumor-specific-cd8-t-cells-by-ex-vivo-pi3k-%C3%AE-inhibition
#10
Rasha Abu-Eid, Shamim Ahmad, Yuan Lin, Mason Webb, Zuzana Berrong, Rajeev K Shrimali, Takumi Kumai, Sudha Ananth, Paulo C Rodriguez, Esteban Celis, John E Janik, Mikayel Mkrtichyan, Samir N Khleif
Inhibition of specific Akt isoforms in CD8+ T cells promotes favored differentiation into memory versus effector cells, the former of which are superior in mediating anti-tumor immunity. In this study, we investigated the role of upstream PI3K isoforms in CD8+ T cell differentiation and assessed the potential use of PI3K isoform-specific inhibitors to favorably condition CD8+ T cells for adoptive cell therapy. The phenotype and proliferative ability of tumor antigen specific CD8+ T cells was assessed in the presence of PI3K-α, -β, or -δ inhibitors...
June 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28614781/cell-lines-generated-from-a-chronic-lymphocytic-leukemia-mouse-model-exhibit-constitutive-btk-and-akt-signaling
#11
Simar Pal Singh, Saravanan Y Pillai, Marjolein J W de Bruijn, Ralph Stadhouders, Odilia B J Corneth, Henk Jan van den Ham, Alice Muggen, Wilfred van IJcken, Erik Slinger, Annemieke Kuil, Marcel Spaargaren, Arnon P Kater, Anton W Langerak, Rudi W Hendriks
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5+ B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEμ CLL mouse model based on sporadic expression of SV40 large T antigen. The cell lines exhibit a stable CD5+CD43+IgM+CD19+ CLL phenotype in culture and can be adoptively transferred into Rag1-/- mice...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604843/alcohol-associated-intestinal-dysbiosis-impairs-pulmonary-host-defense-against-klebsiella-pneumoniae
#12
Derrick R Samuelson, Judd E Shellito, Vincent J Maffei, Eric D Tague, Shawn R Campagna, Eugene E Blanchard, Meng Luo, Christopher M Taylor, Martin J J Ronis, Patricia E Molina, David A Welsh
Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis). To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole) via daily gavage for two weeks...
June 12, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28604557/antigen-presentation-by-individually-transferred-hla-class-i-genes-in-hla-a-hla-b-hla-c-null-human-cell-line-generated-using-the-multiplex-crispr-cas9-system
#13
Cheol-Hwa Hong, Hyun-Jung Sohn, Hyun-Joo Lee, Hyun-Il Cho, Tai-Gyu Kim
Human leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and 3 of HLA-A, HLA-B, and HLA-C genes simultaneously...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28602441/squamous-epithelium-formation-in-the-respiratory-intestine-of-the-bronze-corydoras-corydoras-aeneus-callichthyidae-teleostei
#14
Leszek Satora, Katarzyna Kozioł, Jacek Zebrowski
Accessory respiratory organs in fish exhibit great diversity but share the presence of numerous capillaries covered by a simple squamous epithelium. The adoption of the intestine for respiratory function needs certain special modifications. In this study, we explored immunohistochemical and metabolic fingerprint features that could underlay this adaptation in bronze corydoras Corydoras aeneus. Immunohistochemical localization of the cytoplasmic domain of epidermal growth factor receptor (EGFR) in the respiratory part of intestine demonstrated a strong positive immunoreaction in epithelial cells and connective tissue...
June 8, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28598427/different-populations-of-cd11b-dendritic-cells-drive-th2-responses-in-the-small-intestine-and-colon
#15
Johannes U Mayer, Mimoza Demiri, William W Agace, Andrew S MacDonald, Marcus Svensson-Frej, Simon W Milling
T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4(f/f) CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28598224/mesenchymal-stromal-cells-modulate-macrophages-in-clinically-relevant-lung-injury-models-by-extracellular-vesicle-mitochondrial-transfer
#16
Thomas J Morrison, Megan V Jackson, Erin K Cunningham, Adrien Kissenpfennig, Daniel F McAuley, Cecilia M O'Kane, Anna D Krasnodembskaya
RATIONALE: Acute Respiratory Distress Syndrome (ARDS) remains a major cause of respiratory failure in critically ill patients. Mesenchymal Stromal Cells (MSCs) are a promising candidate for a cell based therapy. However, the mechanisms of MSCs effects in ARDS are not well understood. Here we focused on the paracrine effect of MSCs on macrophage polarization and the role of extracellular vesicle (EV)-mediated mitochondrial transfer. OBJECTIVES: To determine the effects of human MSCs on macrophage function in the ARDS environment and to elucidate the mechanisms of these effects...
June 9, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28595516/cellular-immunotherapy-of-cancer-an-overview-and-future-directions
#17
Ziqi Tao, Shuang Li, Thomas E Ichim, Junbao Yang, Neil Riordan, Venkata Yenugonda, Ivan Babic, Santosh Kesari
The clinical success of checkpoint inhibitors has led to a renaissance of interest in cancer immunotherapies. In particular, the possibility of ex vivo expanding autologous lymphocytes that specifically recognize tumor cells has attracted much research and clinical trial interest. In this review, we discuss the historical background of tumor immunotherapy using cell-based approaches, and provide some rationale for overcoming current barriers to success of autologous immunotherapy. An overview of adoptive transfer of lymphocytes, tumor infiltrating lymphocytes and dendritic cell therapies is provided...
June 2017: Immunotherapy
https://www.readbyqxmd.com/read/28593860/evolving-adoptive-cellular-therapies-in-urological-malignancies
#18
REVIEW
Yien Ning Sophia Wong, Kroopa Joshi, Martin Pule, Karl S Peggs, Charles Swanton, Sergio A Quezada, Mark Linch
Immunotherapies have long been used to treat urological cancers but rarely lead to cure. In the past 5 years, success of immune checkpoint inhibition has led to a resurgence of enthusiasm for immunotherapy in the treatment of solid tumours. Increased understanding of tumour immune biology, technological advancements of gene transfer and cell culture, and improved clinical infrastructures for routine delivery of cell products, has made cell-based immunotherapeutics a real prospect for cancer therapy. These scientific and clinical activities, attempting to exploit the innate and adaptive immune systems for therapeutic gain, are well exemplified by the urological malignancies of renal, bladder, prostate, and penile cancer, a group of anatomically localised diseases, each with a distinct biology and different immunotherapeutic challenges...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28589355/germinal-center-formation-with-retrovirally-transduced-b-cells-for-determining-the-role-of-specific-molecules-in-vivo
#19
Rinako Nakagawa
Retrovirus-mediated gene transfer has become a powerful tool to investigate roles of specific molecules in B cells, due to its efficiency and expeditiousness. This technology is applicable to activated B cells in order to determine effects of a gene of interest during germinal center (GC) reactions in combination with adoptive transfer. To achieve this, B cells derived from SWHEL mice expressing hen egg lysozyme (HEL)-specific B cell receptors (BCR) are stimulated with HEL antigen in vivo and then with anti-CD40 antibody ex vivo...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28588584/protein-arginine-methyltransferase-5-inhibition-upregulates-foxp3-regulatory-t-cells-frequency-and-function-during-the-ulcerative-colitis
#20
Yingxia Zheng, Liya Huang, Wensong Ge, Ming Yang, Yanhui Ma, Guohua Xie, Weiwei Wang, Bingxian Bian, Li Li, Hong Nie, Lisong Shen
Ulcerative colitis (UC) pathogenesis is related to imbalance of immune responses, and the equilibrium between inflammatory T cells and Foxp3(+) regulatory T cells (Tregs) plays an important role in the intestinal homeostasis. Protein arginine methyltransferases (PRMTs) regulate chromatin remodeling and gene expression. Here, we investigated whether inhibition of PRMTs affects colitis pathogenesis in mice and inflammatory bowel disease patients and further explored the underlying mechanisms. In this study, we found that protein arginine N-methyltransferase inhibitor 1 (AMI-1) treatments increased Tregs frequency, function, and reduced colitis incidence...
2017: Frontiers in Immunology
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