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https://www.readbyqxmd.com/read/28819027/combination-therapy-with-bispecific-antibodies-and-pd-1-blockade-enhances-the-antitumor-potency-of-t-cells
#1
Chien-Hsing Chang, Yang Wang, Rongxiu Li, Diane L Rossi, Donglin Liu, Edmund A Rossi, Thomas M Cardillo, David M Goldenberg
The DOCK-AND-LOCK (DNL®) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL® to generate a novel class of trivalent bispecific antibodies (bsAbs), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. Here we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2- and CEACAM5-expressing cancer cells, respectively...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818099/biosemantics-guided-gene-expression-profiling-of-sj%C3%A3-gren-s-syndrome-a-comparative-analysis-with-systemic-lupus-erythematosus-and-rheumatoid-arthritis
#2
Nirav R Shah, Braxton D Noll, Craig B Stevens, Michael T Brennan, Farah B Mougeot, Jean-Luc C Mougeot
BACKGROUND: Sjögren's syndrome (SS) shares many clinical and pathological similarities with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These autoimmune diseases mostly affect women. In this study, concept profile analysis (CPA) and gene expression meta-analysis were used to identify genes potentially involved in SS pathogenesis. METHODS: Human genes associated with SS, SLE, and RA were identified using the CPA tool, Anni 2.1. The differential mRNA expression of genes common to SS and SLE (SS-SLE) was determined in female peripheral blood mononuclear cells (PBMCs) using NCBI-GEO2R...
August 17, 2017: Arthritis Research & Therapy
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
#3
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/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#4
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#5
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28814788/synthesis-of-saccharumoside-b-analogue-with-potential-of-antiproliferative-and-pro-apoptotic-activities
#6
Srinuvasarao Rayavarapu, Nagendra Sastry Yarla, Sunanda Kumari Kadiri, Anupam Bishayee, Siddaiah Vidavalur, Ramu Tadikonda, Mahaboob Basha, Vijaya Rao Pidugu, Kaladhar S V G K Dowluru, Dhananjaya Bhadrapura Lakappa, Mohammad A Kamal, Ghulam Md Ashraf, Vadim V Tarasov, Vladimir N Chubarev, Sergey G Klochkov, George E Barreto, Sergey O Bachurin, Gjumrakch Aliev
A new series of phenolic glycoside esters, saccharumoside-B and its analogs (9b-9n, 10) have been synthesized by the Koenigs-Knorr reaction. Antiproliferative activities of the compounds (9b-9n, 10) were evaluated on various cancer cell lines including, MCF-7 breast, HL-60 leukemia, MIA PaCa-2 pancreatic, DU145 prostate, HeLa cervical and CaCo-2 colon, as well as normal human MCF10A mammary epithelial and human peripheral blood mononuclear cells (PBMC) by MTT assay. Compounds (9b-9n, 10) exhibited considerable antiproliferative effects against cancer cells with IC50 range of 4...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813503/detectable-hiv-rna-in-semen-of-hiv-controllers
#7
Marie-Laure Chaix, Faroudy Boufassa, Candice Meyzer, Marianne Leruez-Ville, Nadia Mahjoub, Marie-Laure Nere, Philippe Genet, Claudine Duvivier, Caroline Lascoux-Combes, Olivier Lambotte, Jade Ghosn
BACKGROUND: Whether spontaneous low levels of HIV-1 RNA in blood plasma correlate with low levels of HIV-1 RNA in seminal plasma has never been investigated in HIV controller (HIC) men so far. METHODS: HIC men enrolled in the ANRS CODEX cohort were eligible for the present study if they had no symptoms of sexually transmitted infections (STI). Two paired samples of blood and semen were collected four weeks apart. HIV-RNA was quantified in blood plasma (bpVL) and in seminal plasma (spVL), and cell-associated HIV-DNA was quantified in peripheral blood mononuclear cells (PBMC) and in non-sperm cells (NSC)...
2017: PloS One
https://www.readbyqxmd.com/read/28812210/increased-il-6-expression-on-thp-1-by-il-34-stimulation-up-regulated-rheumatoid-arthritis-th17-cells
#8
Bing Wang, Yawei Tang, Xiaotong Sun, Xunli Ouyang, Han Li, Jing Wei, Yan Zhang, Xia Li
IL-34 is a pleiotropic cytokine, which is a key regulator of monocytes/macrophages and might participate in the pathogenesis of RA. In this study, we aimed to explore the effect of IL-34 on the monocyte-like cell line THP-1 and the quantitative variation of Th17 cells in THP-1 and RA CD4(+)T cells coculture system. CD4(+)T cells were purified from RA PBMC using immunomagnetic beads. THP-1 were cultured with RA CD4(+)T cells. The frequency of Th17 cells was determined by FACS. Fluorscence indensity and expression of ROS were detected by FACS and cell staining, respectively...
August 15, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28811575/biological-and-functional-characterization-of-bone-marrow-derived-mesenchymal-stromal-cells-from-patients-affected-by-primary-immunodeficiency
#9
Nadia Starc, Daniela Ingo, Antonella Conforti, Valeria Rossella, Luigi Tomao, Angela Pitisci, Fabiola De Mattia, Immacolata Brigida, Mattia Algeri, Mauro Montanari, Giuseppe Palumbo, Pietro Merli, Paolo Rossi, Alessandro Aiuti, Franco Locatelli, Maria Ester Bernardo
Mesenchymal stromal cells (MSCs) represent a key component of bone marrow (BM) microenvironment and display immune-regulatory properties. We performed a detailed analysis of biological/functional properties of BM-MSCs derived from 33 pediatric patients affected by primary immune-deficiencies (PID-MSCs): 7 Chronic Granulomatous Disease (CGD), 15 Wiskott-Aldrich Syndrome (WAS), 11 Severe Combined Immunodeficiency (SCID). Results were compared with MSCs from 15 age-matched pediatric healthy-donors (HD-MSCs). Clonogenic and proliferative capacity, differentiation ability, immunophenotype, immunomodulatory properties were analyzed...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808220/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#10
Xunxian Liu, Zemin Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807607/plasma-cell-and-serum-antibody-responses-to-influenza-vaccine-in-preterm-and-full-term-infants
#11
Carl T D'Angio, Claire P Wyman, Ravi S Misra, Jessica L Halliley, Hongyue Wang, Julianne E Hunn, Caitlin M Fallone, F Eun-Hyung Lee
BACKGROUND: Preterm (PT) infants are at greater risk for severe influenza infection and experience decrements in long-term antibody responses to vaccines. This may related to defects in antibody secreting cell (ASC) generation. OBJECTIVE: To investigate the relationships among the frequencies of influenza-specific antibody secreting cells, ASC numbers and subsets, and antibody responses to influenza vaccines (IV) among PT and full-term (FT) infants. DESIGN/METHODS: We enrolled 11 former PT (≤32weeks' gestation, ≤1500 g' birth weight) and 11FT infants, 6-17months of age, receiving their first influenza immunizations...
August 11, 2017: Vaccine
https://www.readbyqxmd.com/read/28805308/lymphocyte-profile-and-cytokine-mrna-expression-in-peripheral-blood-mononuclear-cells-of-patients-with-recurrent-respiratory-papillomatosis-suggest-dysregulated-cytokine-mrna-response-and-impaired-cytotoxic-capacity
#12
Anna Holm, Olga Nagaeva, Ivan Nagaev, Christos Loizou, Göran Laurell, Lucia Mincheva-Nilsson, Karin Nylander, Katarina Olofsson
OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is a relatively rare, chronic disease caused by Human Papilloma Virus (HPV) 6 and 11, and characterized by wart-like lesions in the airway affecting voice and respiratory function. The majority of HPV infections are asymptomatic and resolve spontaneously, however, some individuals are afflicted with persistent HPV infections. Failure to eliminate HPV 6 and 11 due to a defect immune responsiveness to these specific genotypes is proposed to play a major role in the development of RRP...
August 14, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28805233/analytic-and-dynamic-secretory-profile-of-patient-derived-cytokine-induced-killer-cells
#13
Giulia Mesiano, Roberta Zini, Giulia Montagner, Nicoletta Bianchi, Rossella Manfredini, Antonella Chillemi, Massimo Aglietta, Giovanni Grignani, Ilaria Lampronti, Erika Fiorino, Fabio Malavasi, Dario Sangiolo, Roberto Gambari, Davide Ferrari
Adoptive immunotherapy with Cytokine Induced Killer (CIK) cells has shown antitumor activity against several kinds of cancers in preclinical models and clinical trials. CIK cells are a subset of ex vivo expanded T lymphocytes with T-NK phenotype and MHC-unrestricted antitumor activity. Literature provides scanty information on cytokines, chemokines and growth factors secreted by CIK cells. Therefore, we investigated the secretory profile of CIK cells generated from tumor patients. The secretome analysis was performed at specific time points (day 1, day 14 and day 21) of CIK cells expansion...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28803951/monocytes-inhibit-hepatitis-c-virus-induced-trail-expression-on-cd56-bright-nk-cells
#14
Dalila Mele, Stefania Mantovani, Barbara Oliviero, Giulia Grossi, Andrea Lombardi, Mario U Mondelli, Stefania Varchetta
BACKGROUND AND AIMS: Natural killer (NK) cells play an important role in the pathogenesis of HCV infection. We have previously shown that culture-derived HCV (HCVcc) enhance tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) expression on healthy but not on HCV-infected patient-derived NK cells, which was likely dependent on accessory cells. Here we sought mechanistic insights involved in altered TRAIL upregulation in this setting. METHODS: Peripheral blood mononuclear cells (PBMC) from controls and HCV-infected patients were exposed to HCVcc...
August 10, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28802860/upregulation-of-il-9-and-jak-stat-signaling-pathway-in-children-with-autism
#15
Sheikh F Ahmad, Ahmed Nadeem, Mushtaq A Ansari, Saleh A Bakheet, Laila Yousef Al-Ayadhi, Sabry M Attia
Autism spectrum disorder (ASD) gradually develops predominantly neurodevelopmental disorders, which are socially diagnosed in early childhood. Though the etiopathology of ASD is not clear, immune alteration has been suggested as autism's pathophysiological mechanism. Previous studies found that several cytokines and transcription factor activation pathways were significantly increased in ASD. IL-9 has been confirmed to play a significant role in the central nervous system (CNS). The aim of the present study was to investigate the understudied role of pro- and anti-inflammatory cytokines and the JAK-STAT signaling pathway in ASD...
August 9, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28802400/mycobacterium-tuberculosis-myma-is-a-tlr2-agonist-that-activate-macrophages-and-a-th1-response
#16
Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma
Cell wall of Mycobacterium tuberculosis (M.tb) is a major source of immunogenic proteins that can be tested as vaccine candidates. MymA (Rv3083), a 55 kDa M.tb flavin containing monooxygenase, is involved in modification of mycolic acids during acidic shock following M.tb internalization in macrophage. In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) engagement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28797995/tinospora-cordifolia-induces-cell-cycle-arrest-in-human-oral-squamous-cell-carcinoma-cells
#17
Parveen Bansal, Manzoor Ahmad Malik, Satya N Das, Jasbir Kaur
Natural products with medicinal value are gradually gaining importance in clinical research due to their well-known property of no side effects as compared to drugs. Tinospora cordifolia (Guduchi) has been used for centuries in Ayurvedic system of medicine for treating various ailments including cancer. In present study, we found that the Tinospora cordifolia extracts (TCE) induced inhibition of proliferation of KB cells was associated with arrest of G0/G1-phase of cell cycle. The effectiveness of TCE in checking the growth of KB cells without altering the growth of normal peripheral blood mononuclear cells (PBMC) indicates that Tinospora cordifolia has differential effect on normal and malignant cells hence, it may have therapeutic potential in cancer...
May 2017: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28796240/glucocorticoid-receptor-expression-on-circulating-leukocytes-in-healthy-and-asthmatic-adolescents-in-response-to-exercise
#18
Kim D Lu, Dan Cooper, Fadia Haddad, Frank Zaldivar, Monica Kraft, Shlomit Radom-Aizik
BackgroundPoor aerobic fitness is associated with worsening of asthma symptoms, and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes, reflecting a reduced responsiveness to stress.MethodsIn a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to an acute exercise challenge before and after the exercise training intervention...
August 2017: Pediatric Research
https://www.readbyqxmd.com/read/28795366/ru-ii-diphenylphosphine-pyridine-6-thiolate-complexes-induce-s-180-cell-apoptosis-through-intrinsic-mitochondrial-pathway-involving-inhibition-of-bcl-2-and-p53-bax-activation
#19
Wanessa Carvalho Pires, Benedicto Augusto Vieira Lima, Flávia de Castro Pereira, Aliny Pereira Lima, Francyelli Mello-Andrade, Hugo Delleon Silva, Monize Martins da Silva, Legna Colina-Vegas, Javier Ellena, Alzir A Batista, Elisângela de Paul Silveira-Lacerda
The aim of this work was the synthesis, characterization, and cytotoxicity evaluation of three new Ru(II) complexes with a general formula [Ru(Spy)(bipy)(P-P)]PF6 [Spy = pyridine-6-thiolate; bipy = 2,2'-bipyridine; P-P = 1,2-bis(diphenylphosphine)ethane (1); 1,3-bis(diphenylphosphine) propane (2); and 1,1'-bis(diphenylphosphino)ferrocene] (4). Complex (3) with the 1,4-bis(diphenylphosphine)butane ligand, already known from the literature, was also synthesized, to be better studied here. The cytotoxicities of the complexes toward two kinds of cancerous cells (K562 and S-180 cells) were evaluated and compared to normal cells (L-929 and PBMC) by MTT assay...
August 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28793772/effect-of-dietary-lipids-on-endotoxemia-influences-postprandial-inflammatory-response
#20
Javier Lopez-Moreno, Sonia García-Carpintero, Rosa Jimenez-Lucena, Carmen Haro, Oriol A Rangel-Zúñiga, Ruth Blanco-Rojo, Elena Maria Yubero-Serrano, Francisco J Tinahones, Javier Delgado-Lista, Pablo Pérez-Martínez, Helen M Roche, Jose Lopez-Miranda, Antonio Camargo
Metabolic syndrome (MetS) results in postprandial metabolic alterations that predisposes to a state of chronic low-grade inflammation and increased oxidative stress. We aimed to assess the effect of the consumption of the quantity and quality of dietary fat on fasting and postprandial plasma lipopolysaccharides (LPS). A subgroup of 75 subjects with metabolic syndrome was randomized to receive 1 of 4 diets: HSFA, rich in saturated fat; HMUFA, rich in monounsaturated fat; LFHCC n-3, low-fat, rich in complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids; LFHCC low-fat, rich in complex carbohydrate diet supplemented with placebo, for 12 week each...
August 9, 2017: Journal of Agricultural and Food Chemistry
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