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cytotoxic t cell therapy

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https://www.readbyqxmd.com/read/28820897/persistent-infection-due-to-a-small-colony-variant-of-burkholderia-pseudomallei-leads-to-pd-1-upregulation-on-circulating-immune-cells-and-mononuclear-infiltration-in-viscera-of-experimental-balb-c-mice
#1
Jia-Xiang See, Samudi Chandramathi, Mahmood Ameen Abdulla, Jamuna Vadivelu, Esaki M Shankar
BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes...
August 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28820501/interleukin-armed-chimeric-antigen-receptor-modified-t-cells-for-cancer-immunotherapy
#2
REVIEW
Y Huang, D Li, D-Y Qin, H-F Gou, W Wei, Y-S Wang, Y-Q Wei, W Wang
Chimeric antigen receptor-modified T cells (CAR-T) are endowed with cytotoxic specificity to tumor cells. Although CAR-T-based cancer immunotherapy presents curable therapeutic potential for hematological malignancies, achieving substantial efficacy for solid tumors remain challenging. Researchers have exploited many strategies to enhance the anti-tumor efficacy of CAR-T cells for solid tumors, among which cytokine-armed CAR-T cells improve the proliferation, survival, homing and other properties of CAR-T cells...
August 18, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28819024/trastuzumab-increases-her2-uptake-and-cross-presentation-by-dendritic-cells
#3
Victor A Gall, Anne V Philips, Na Qiao, Karen Clise-Dwyer, Alexander A Perakis, Mao Zhang, Guy Travis Clifton, Pariya Sukhumalchandra, Qing Ma, Sangeetha M Reddy, Dihua Yu, Jeffrey J Molldrem, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf
Early phase clinical trials evaluating CD8+ T cell-eliciting, HER2-derived peptide vaccines administered to HER2-positive breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the monoclonal antibody targeting the HER2 protein. Among 60 patients enrolled on clinical trials evaluating the E75+GM-CSF and GP2+GM-CSF vaccines, there have been no recurrences in patients vaccinated after receiving trastuzumab as part of standard therapy in the per treatment analyses conducted after a median follow-up of greater than 34 months...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818060/rna-transfection-of-%C3%AE-%C3%AE-t-cells-with-a-chimeric-antigen-receptor-or-an-%C3%AE-%C3%AE-t-cell-receptor-a-safer-alternative-to-genetically-engineered-%C3%AE-%C3%AE-t-cells-for-the-immunotherapy-of-melanoma
#4
Dennis C Harrer, Bianca Simon, Shin-Ichiro Fujii, Kanako Shimizu, Ugur Uslu, Gerold Schuler, Kerstin F Gerer, Stefanie Hoyer, Jan Dörrie, Niels Schaft
BACKGROUND: Adoptive T-cell therapy relying on conventional T cells transduced with T-cell receptors (TCRs) or chimeric antigen receptors (CARs) has caused substantial tumor regression in several clinical trials. However, genetically engineered T cells have been associated with serious side-effects due to off-target toxicities and massive cytokine release. To obviate these concerns, we established a protocol adaptable to GMP to expand and transiently transfect γ/δ T cells with mRNA...
August 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#5
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28804660/large-granular-lymphocytic-leukemia-a-report-of-response-to-rituximab
#6
Uroosa Ibrahim, Sara Parylo, Shiksha Kedia, Shafinaz Hussein, Jean Paul Atallah
Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28800119/new-insights-contributing-to-the-development-of-effective-vaccines-and-therapies-to-reduce-the-pathology-caused-by-hrsv
#7
REVIEW
Nicolás M S Gálvez, Jorge A Soto, Alexis M Kalergis
Human Respiratory Syncytial Virus (hRSV) is one of the major causes of acute lower respiratory tract infections (ALRTI) worldwide, leading to significant levels of immunocompromisation as well as morbidity and mortality in infants. Its main target of infection is the ciliated epithelium of the lungs and the host immune responses elicited is ineffective at achieving viral clearance. It is thought that the lack of effective immunity against hRSV is due in part to the activity of several viral proteins that modulate the host immune response, enhancing a Th2-like pro-inflammatory state, with the secretion of cytokines that promote the infiltration of immune cells to the lungs, with consequent damage...
August 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28798777/mesenchymal-stem-cells-promote-metastasis-of-lung-cancer-cells-by-downregulating-systemic-antitumor-immune-response
#8
Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Maja Misirkic-Marjanovic, Valentin Djonov, Vladimir Jakovljevic, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28798327/assessing-cell-nanoparticle-interactions-by-high-content-imaging-of-biocompatible-iron-oxide-nanoparticles-as-potential-contrast-agents-for-magnetic-resonance-imaging
#9
Roxanne Hachani, Martin A Birchall, Mark W Lowdell, Georgios Kasparis, Le D Tung, Bella B Manshian, Stefaan J Soenen, Willy Gsell, Uwe Himmelreich, Codi A Gharagouzloo, Srinivas Sridhar, Nguyen T K Thanh
Stem cell tracking in cellular therapy and regenerative medicine is an urgent need, superparamagnetic iron oxide nanoparticles (IONPs) could be used as contrast agents in magnetic resonance imaging (MRI) that allows visualization of the implanted cells ensuring they reach the desired sites in vivo. Herein, we report the study of the interaction of 3,4-dihydroxyhydrocinnamic acid (DHCA) functionalized IONPs that have desirable properties for T2 - weighted MRI, with bone marrow-derived primary human mesenchymal stem cells (hMSCs)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794626/folic-acid-functionalized-polyethylenimine-superparamagnetic-iron-oxide-nanoparticles-as-theranostic-agents-for-magnetic-resonance-imaging-and-pd-l1-sirna-delivery-for-gastric-cancer
#10
Xin Luo, Xia Peng, Jingying Hou, Shuyun Wu, Jun Shen, Lingyun Wang
Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)-polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28791124/combining-dendritic-cells-and-b-cells-for-presentation-of-oxidised-tumour-antigens-to-cd8-t-cells
#11
Melanie L Grant, Nicholas Shields, Silke Neumann, Katrin Kramer, Andrea Bonato, Christopher Jackson, Margaret A Baird, Sarah L Young
The dendritic cell (DC) is the foremost antigen-presenting cell (APC) for ex vivo expansion of tumour-specific patient T cells. Despite marked responses in some patients following reinfusion of DC-activated autologous or HLA-matched donor T cells, overall response rates remain modest in solid tumours. Furthermore, most studies aim to generate immune responses against defined tumour-associated antigens (TAA), however, meta-analysis reveals that those approaches have less clinical success than those using whole tumour cells or their components...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28781967/immunotherapeutic-strategies-for-gastric-carcinoma-a-review-of-preclinical-and-clinical-recent-development
#12
REVIEW
Mohamed Abozeid, Antonio Rosato, Roberta Sommaggio
Gastric carcinoma (GC) is the 2nd most common cause of cancer-related death. Despite advances in conventional treatment and surgical interventions, a high percentage of GC patients still have poor survival. Recently, immunotherapy has become a promising approach to treat GC. Here, we present preclinical and clinical studies encouraging the use of vaccination, adoptive T-cell therapy (ACT), and immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28780888/anti-gd2-immunotherapy-for-neuroblastomas
#13
Sameer Sait, Shakeel I Modak
Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy. Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development...
August 7, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28780376/retinoic-acid-induction-of-cd1d-expression-primes-chronic-lymphocytic-leukemia-b-cells-for-killing-by-cd8-invariant-natural-killer-t-cells
#14
Yasmeen G Ghnewa, Vincent P O'Reilly, Elisabeth Vandenberghe, Paul V Browne, Anthony M McElligott, Derek G Doherty
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28780074/intra-hepatic-depletion-of-mucosal-associated-invariant-t-cells-in-hepatitis-c-virus-induced-liver-inflammation
#15
Fabian J Bolte, Ashley C O'Keefe, Lauren M Webb, Elisavet Serti, Elenita Rivera, T Jake Liang, Marc Ghany, Barbara Rehermann
BACKGROUND & AIMS: Chronic hepatitis affects phenotypes of innate and adaptive immune cells. Mucosal associated invariant T (MAIT) cells are enriched in the liver as compared to the blood, respond to intra-hepatic cytokines, and (via the semi-invariant T-cell receptor) to bacteria translocated from the gut. Little is known about the role of MAIT cells in livers of patients with chronic hepatitis C virus (HCV) infection and their fate after antiviral therapy. METHODS: We collected blood samples from 42 patients with chronic HCV infection who achieved a sustained virologic response after 12 weeks of treatment with sofosbuvir and velpatasvir...
August 2, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28777668/therapeutic-tumor-control-of-her2-dna-vaccines-is-achieved-by-an-alteration-of-tumor-cells-and-tumor-microenvironment-by-gemcitabine-and-anti-gr-1-ab-treatment-in-a-her2-expressing-tumor-model
#16
Sayyed Nilofar Danishmalik, Jeong-Im Sin
Therapeutic control of tumors is challenging as they tend to alter their biological functions and microenvironment. In a CT26/HER2 tumor model, HER2 DNA vaccines and even anti-PD-L1 Abs failed to display antitumor therapeutic activity while inducing Ag-specific cytotoxic T lymphocyte (CTL) activity. To clarify this contradictory finding, we selected tumor cells (CT26/HER2-1) from one tumor-bearing animal in the therapeutic model. CT26/HER2-1 cells behaved similar to wild-type CT26/HER2 cells in their HER2 expression, immune cell stimulation for IFN-γ production, and antitumor immune sensitivity...
August 4, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28777460/phosphatidylinositol-3-kinase-inhibition-potentiates-glucocorticoid-response-in-b-cell-acute-lymphoblastic-leukemia
#17
Cecilia Evangelisti, Alessandra Cappellini, Mariana Oliveira, Rita Fragoso, João T Barata, Alice Bertaina, Franco Locatelli, Carolina Simioni, Luca M Neri, Francesca Chiarini, Annalisa Lonetti, Francesca Buontempo, Ester Orsini, Andrea Pession, Lucia Manzoli, Alberto Maria Martelli, Camilla Evangelisti
Despite remarkable progress in polychemotherapy protocols, pediatric B-cell acute lymphoblastic leukemia (B-ALL) remains fatal in around 20% of cases. Hence, novel targeted therapies are needed for patients with poor prognosis. Glucocorticoids (GCs) are drugs commonly administrated for B-ALL treatment. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling pathway is frequently observed in B-ALL and contributes to GC-resistance. Here, we analyzed for the first time to our knowledge, the therapeutic potential of pan and isoform-selective PI3K p110 inhibitors, alone or combined with dexamethasone (DEX), in B-ALL leukemia cell lines and patient samples...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28769806/a-red-blood-cell-membrane-camouflaged-nanoparticle-counteracts-streptolysin-o-mediated-virulence-phenotypes-of-invasive-group-a-streptococcus
#18
Tamara Escajadillo, Joshua Olson, Brian T Luk, Liangfang Zhang, Victor Nizet
Group A Streptococcus (GAS), an important human-specific Gram-positive bacterial pathogen, is associated with a broad spectrum of disease, ranging from mild superficial infections such as pharyngitis and impetigo, to serious invasive infections including necrotizing fasciitis and streptococcal toxic shock syndrome. The GAS pore-forming streptolysin O (SLO) is a well characterized virulence factor produced by nearly all GAS clinical isolates. High level expression of SLO is epidemiologically linked to intercontinental dissemination of hypervirulent clonotypes and poor clinical outcomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28765552/antitumoral-effects-of-%C3%AE-cdcpli-a-pla2-inhibitor-from-crotalus-durissus-collilineatus-via-pi3k-akt-pathway-on-mda-mb-231-breast-cancer-cell
#19
Sarah N C Gimenes, Daiana S Lopes, Patrícia T Alves, Fernanda V P V Azevedo, Lara Vecchi, Luiz R Goulart, Thais C S Rodrigues, André L Q Santos, Vera L de C Brites, Thaise L Teixeira, Cláudio V da Silva, Matheus H Dias, Samuel C Teixeira, Renata S Rodrigues, Kelly A G Yoneyama, Ricardo A Oliveira, Veridiana de M Rodrigues
Phospholipases A2 (PLA2s) overexpression is closely associated with the malignant potential of breast cancers. Here, we showed for the first the antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 cell. Firstly, γCdcPLI was more cytotoxic to MDA-MB-231 breast cancer cells than other cell lines (MCF-7, HeLa, PC3 and A549) and did not affect the viability of non-tumorigenic breast cell (MCF 10A). In addition, γCdcPLI induced modulation of important mediators of apoptosis pathways such as p53, MAPK-ERK, BIRC5 and MDM2...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28762951/immunomodulatory-and-antitumor-effects-of-type-i-interferons-and-their-application-in-cancer-therapy
#20
REVIEW
Ruan F V Medrano, Aline Hunger, Samir Andrade Mendonça, José Alexandre M Barbuto, Bryan E Strauss
During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes...
July 25, 2017: Oncotarget
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