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https://www.readbyqxmd.com/read/28729866/cytokine-induced-killer-cells-as-pharmacological-tools-for-cancer-immunotherapy
#1
REVIEW
Xingchun Gao, Yajing Mi, Na Guo, Hao Xu, Lixian Xu, Xingchun Gou, Weilin Jin
Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3(+)CD56(+) natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28726516/targeting-nsg-mice-engrafting-cells-with-a-clinically-applicable-lentiviral-vector-corrects-osteoclasts-in-infantile-malignant-osteopetrosis
#2
Ilana Moscatelli, Henrik Löfvall, Christian Schneider Thudium, Michael Rothe, Carmen Montano, Zsuzsanna Kertész, Mehtap Sirin, Ansgar Schulz, Axel Schambach, Kim Henriksen, Johan Richter
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically applicable lentiviral vector expressing TCIRG1 to correct osteoclast function in IMO. We compared two mammalian promoters: elongation factor 1α short promoter (EFS) and chimeric myeloid promoter (ChimP). EFS was chosen for continued experiments as it performed better...
July 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28725483/engineering-glucose-metabolism-of-escherichia-coli-under-nitrogen-starvation
#3
Victor Chubukov, John James Desmarais, George Wang, Leanne Jade G Chan, Edward Ek Baidoo, Christopher J Petzold, Jay D Keasling, Aindrila Mukhopadhyay
A major aspect of microbial metabolic engineering is the development of chassis hosts that have favorable global metabolic phenotypes, and can be further engineered to produce a variety of compounds. In this work, we focus on the problem of decoupling growth and production in the model bacterium Escherichia coli, and in particular on the maintenance of active metabolism during nitrogen-limited stationary phase. We find that by overexpressing the enzyme PtsI, a component of the glucose uptake system that is inhibited by α-ketoglutarate during nitrogen limitation, we are able to achieve a fourfold increase in metabolic rates...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28725432/transplanters-drive-cars-to-the-clinic-by-brewing-ice-t-the-moffitt-roadmap
#4
EDITORIAL
Frederick L Locke, Claudio Anasetti
Recent single institution clinical trial successes with anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies attracted significant attention from industry. Our center sought to rapidly and safely bring industry sponsored pivotal trials to our patients and to prepare for additional cell therapy trials in solid and liquid tumors from both industry and our own investigators. We implemented a collaborative cross departmental program to provide clinical care and trial coordination for immune cell therapies...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-anti-tumor-activity
#5
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T-cells against leukemia and lymphoma with promising clinical results.(1-3) Extending this approach to allogeneic T-cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28725038/genomic-characterization-of-novel-incfii-type-multidrug-resistant-plasmids-p0716-kpc-and-p12181-kpc-from-klebsiella-pneumoniae
#6
Jiao Feng, Zhe Yin, Qiangyuan Zhao, Yachao Zhao, Defu Zhang, Xiaoyuan Jiang, Weili Wu, Weijun Chen, Hui Wang, Yajun Song, Yigang Tong, Jinglin Wang, Yanjun Li, Dongsheng Zhou
This study aimed to genetically characterize two fully-sequenced novel IncFII-type multidrug resistant (MDR) plasmids, p0716-KPC and p12181-KPC, recovered from two different clinical Klebsiella pneumoniae isolates. p0716-KPC and p12181-KPC had a very similar genomic content. The backbones of p0716-KPC/p12181-KPC contained two different replicons (belonging to a novel IncFII subtype and the Rep_3 family), the IncFIIK and IncFIIY maintenance regions, and conjugal transfer gene sets from IncFIIK-type plasmids and unknown origins...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#7
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28724560/accurate-detection-of-methicillin-resistant-staphylococcus-aureus-in-mixtures-utilizing-single-bacterial-duplex-droplet-digital-pcr
#8
Jun Luo, Junhua Li, Hang Yang, Junping Yu, Hongping Wei
Accurate and rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) is needed to screen MRSA carriers and improve treatment. The current widely used duplex PCR methods are not able to differentiate MRSA from the co-existence of methicillin-susceptible S. aureus (MSSA) and other methicillin-resistant Staphylococci In this study, we aimed to develop a direct method for accurate and rapid detection of MRSA in clinical samples from open environments, such as nasal swab. The new molecular assay is based on detecting the co-occurrence of nuc and mecA markers in a single bacterial cell by utilizing droplet digital PCR (ddPCR) with a chimeric lysin ClyH for cell lysis...
July 19, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28724556/performance-assessment-of-a-trypanosoma-cruzi-chimeric-antigen-in-multiplex-liquid-microarray-assays
#9
Fred Luciano Neves Santos, Paola Alejandra Fiorani Celedon, Nilson Ivo Tonin Zanchin, Amanda Leitolis, Sandra Crestani, Leonardo Foti, Wayner Vieira de Souza, Yara de Miranda Gomes, Marco Aurélio Krieger
Diagnosing chronic Chagas disease (CD) requires antibody--antigen detection methods, traditionally based on enzymatic assay techniques whose performance depend on the type and quality of antigen used. Previously, 4 recombinant chimeric proteins from Instituto de Biologia Molecular do Paraná (IBMP-8.1 to -8.4) comprising immuno-dominant regions of diverse Trypanosoma cruzi antigens showed excellent diagnostic performance in enzyme-linked immunosorbent assays. Considering that next-generation platforms offer improved CD diagnostic accuracy with different T...
July 19, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28724261/development-of-a-sandwich-enzyme-linked-immunosorbent-assay-for-dtmp-gh-fusion-protein-by-rational-immunogen-selection
#10
Song Wang, Mingqiang Shen, Shilei Chen, Cheng Wang, Fang Chen, Mo Chen, Gaomei Zhao, Xinze Ran, Tianmin Cheng, Yongping Su, Yang Xu, Junping Wang
dTMP-GH is a chimeric protein containing a tandem dimer of thrombopoietin mimetic peptide (dTMP) fused to human growth hormone (hGH) prepared previously by our team. It shows significant bioactivity in promoting thrombocytopoiesis, but detection of intact dTMP-GH in plasma is still a challenge due to the presence of endogenous hGH. In this study, a rabbit polyclonal antibody with high affinity to dTMP was obtained with a BSA-conjugated immunogen composed of 20 amino acids sequence spanning two TMP and the linker...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#11
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
July 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28720651/interspecies-chimeras-for-human-stem-cell-research
#12
Hideki Masaki, Hiromitsu Nakauchi
Interspecies chimeric assays are a valuable tool for investigating the potential of human stem and progenitor cells, as well as their differentiated progeny. This Spotlight article discusses the different factors that affect interspecies chimera generation, such as evolutionary distance, developmental timing, and apoptosis of the transplanted cells, and suggests some possible strategies to address them. A refined approach to generating interspecies chimeras could contribute not only to a better understanding of cellular potential, but also to understanding the nature of xenogeneic barriers and mechanisms of heterochronicity, to modeling human development, and to the creation of human transplantable organs...
July 15, 2017: Development
https://www.readbyqxmd.com/read/28720382/activated-leukocyte-cell-adhesion-molecule-is-involved-in-excitatory-synaptic-transmission-and-plasticity-in-the-rat-spinal-dorsal-horn
#13
Eun-Sung Park, Sang-Min Jeon, Haein Weon, Hee-Jung Cho, Dong-Ho Youn
Activated leukocyte cell adhesion molecule (ALCAM), a member of type I transmembrane immunoglobulin superfamily of cell adhesion molecule, is expressed in the surface membrane of various cell types including neurons. In the spinal cord dorsal horn (DH), the first gate for the sensory and pain transmission to the brain, the expression and function of ALCAM have not been known yet. Therefore, we here investigate the synaptic function of ALCAM in the substantia gelatinosa (lamina II) of the spinal DH, as well as its expression in the DH...
July 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28719798/chimeric-antigen-receptor-t-cells-for-b-cell-malignancies
#14
REVIEW
Eben I Lichtman, Gianpietro Dotti
The adoptive transfer of T-lymphocytes modified to express chimeric antigen receptors (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies. This has led to a rapid expansion in the number of clinical trials over the past several years. Although CD19-specific CAR-Ts are the most extensively evaluated, CAR-Ts specific for other B-cell-associated targets have also shown promise. However, despite this success, toxicities associated with CAR-T administration remain a significant concern...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28719653/isolation-of-a-monoclonal-antibody-from-a-phage-display-library-binding-the-rhesus-macaque-mhc-class-i-allomorph-mamu-a1-001
#15
Nathan Holman, Jason T Weinfurter, Trevor R Harsla, Roger W Wiseman, Aaron J Belli, Anthony J Michaels, Keith A Reimann, Robert I DeMars, Matthew R Reynolds
Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001...
2017: PloS One
https://www.readbyqxmd.com/read/28719400/dengue-vaccines-implications-for-dengue-control
#16
Matthew L Robinson, Anna P Durbin
PURPOSE OF REVIEW: Dengue, the most common arbovirus, is an increasingly significant cause of morbidity worldwide. After decades of research, an approved tetravalent dengue vaccine is finally available. Models constructed using recently available vaccine efficacy data allow for a data-driven discussion of the potential impact of dengue vaccine deployment on global control. RECENT FINDINGS: Phase 3 efficacy trials demonstrated that the approved dengue vaccine, chimeric yellow fever-dengue-tetravalent dengue vaccine, has an efficacy of 60% against dengue illness of any severity...
July 14, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28718815/regional-delivery-of-chimeric-antigen-receptor-car-t-cells-for-cancer-therapy
#17
REVIEW
Praveen Sridhar, Fabio Petrocca
Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery...
July 18, 2017: Cancers
https://www.readbyqxmd.com/read/28717938/rituximab-in-steroid-sensitive-nephrotic-syndrome-lessons-from-clinical-trials
#18
REVIEW
Kazumoto Iijima, Mayumi Sako, Koichi Kamei, Kandai Nozu
Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. A total of 80-90% of patients with childhood idiopathic nephrotic syndrome achieve remission with steroid therapy [steroid-sensitive nephrotic syndrome (SSNS)]. However, approximately 50% of children with SSNS develop frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS or SDNS are usually treated with immunosuppressive agents, but 10-20% of children receiving immunosuppressive agents still show frequent relapses or steroid dependence during or after treatment, defined as complicated FRNS or SDNS...
July 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28717420/comprehensive-toxicity-and-immunogenicity-studies-reveal-minimal-effects-in-mice-following-sustained-dosing-of-extracellular-vesicles-derived-from-hek293t-cells
#19
Xiaohua Zhu, Mohamed Badawi, Steven Pomeroy, Dhruvitkumar S Sutaria, Zhiliang Xie, Alice Baek, Jinmai Jiang, Ola A Elgamal, Xiaokui Mo, Krista La Perle, Jeffrey Chalmers, Thomas D Schmittgen, Mitch A Phelps
Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced EV clearance. Furthermore, EVs from different cell sources or EVs comprising various cargo may differ with respect to immunogenicity or toxicity. To assess EV-induced immune response and toxicity, we dosed C57BL/6 mice with EVs intravenously and intraperitoneally for 3 weeks...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28716950/analysis-of-small-critical-regions-of-swi1-conferring-prion-formation-maintenance-and-transmission
#20
Stephanie Valtierra, Zhiqiang Du, Liming Li
Saccharomyces cerevisiae contains several prion elements, which are epigenetically transmitted as self-perpetuating protein conformations. One such prion is [SWI(+) ], whose protein determinant is Swi1, a subunit of the SWI/SNF chromatin-remodeling complex. We previously reported that [SWI(+) ] formation results in a partial loss-of-function phenotype of poor growth in non-glucose media and abolishment of multicellularity. We also showed that the first 38 amino acids of Swi1 propagated [SWI(+)]. We show here that a region as small as the first 32 amino acids of Swi1 (Swi11-32) can decorate [SWI(+)] aggregation and stably maintain and transmit [SWI(+)] independently of full-length Swi1...
July 17, 2017: Molecular and Cellular Biology
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