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https://www.readbyqxmd.com/read/28822771/pge2-pulsing-of-murine-bone-marrow-cells-reduces-migration-of-daughter-monocytes-macrophages-in-vitro-and-in-vivo
#1
Terence A McGonigle, Amy R Dwyer, Eloise L Greenland, Naomi M Scott, Kevin N Keane, Philip Newsholme, Helen S Goodridge, Leonard I Zon, Fiona J Pixley, Prue H Hart
Monocytes/macrophages differentiating from bone marrow cells pulsed for 2 hours at 37(o)C with a stabilised derivative of prostaglandin E2, 16,16-dimethyl PGE2 (dmPGE2), migrated less efficiently towards a chemoattractant than monocytes/macrophages differentiated from bone marrow cells pulsed with vehicle. To confirm that the effect on bone marrow cells was long-lasting and to replicate human bone marrow transplantation, chimeric mice were established with donor bone marrow cells pulsed for 2 hours with dmPGE2 before injection into marrow-ablated congenic recipient mice...
August 16, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28822103/current-progress-in-innovative-engineered-antibodies
#2
REVIEW
William R Strohl
As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year...
August 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28821758/how-to-achieve-tat-transport-with-alien-tata
#3
René Steffen Hauer, Roland Freudl, Julia Dittmar, Mario Jakob, Ralf Bernd Klösgen
TatA is an essential and structurally conserved component of all known Twin-arginine transport (Tat) machineries which are able to catalyse membrane transport of fully folded proteins. Here we have investigated if bacterial TatA, or chimeric pea/E. coli TatA derivatives, are capable of replacing thylakoidal TatA in function. While authentic E. coli TatA does not show any transport activity in thylakoid transport experiments, TatA chimeras comprising the transmembrane helix (TMH) of pea TatA are fully active...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821531/cd28-and-41bb-costimulation-enhances-the-effector-function-of-cd19-specific-engager-t-cells
#4
Mireya Paulina Velasquez, Arpad Szoor, Abishek Vaidya, Aarohi Thakkar, Phuong Nguyen, Meng-Fen Wu, Hao Liu, Stephen Gottschalk
T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3zeta and CD28 or 41BB have potent antitumor activity in early phase clinical studies for B-cell malignancies. Besides CD19-specific CARs, other approaches are actively being pursued to redirect T cells to CD19, including recombinant bispecific T-cell engager (BiTE) proteins or T cells genetically modified to express BiTEs (engager [ENG] T cells). Since BiTEs provide no costimulation, we investigated here if provision of costimulation through CD28 and 41BB enhances the effector function of CD19-ENG T cells...
August 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28821272/novel-immunotherapies-for-adult-patients-with-b-lineage-acute-lymphoblastic-leukemia
#5
REVIEW
Guoqing Wei, Jiasheng Wang, He Huang, Yanmin Zhao
The past decade witnessed the rapid development of adult B-lineage acute lymphoblastic leukemia (ALL) treatment. Beyond the development of chemotherapy regimens, immunotherapy is starting a new era with unprecedented complete remission (CR) rate. Targeting B-lineage-specific surface markers such as CD19, CD20, CD22, or CD52, immunotherapy has been demonstrating promising clinical results. Among the immunotherapeutic methods, naked monoclonal antibodies (mAbs), antibody-drug conjugate (ADC), bispecific T cell engager (BiTE), and chimeric antigen receptor (CAR) T cells are the main types...
August 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28820715/limited-transmission-potential-of-takeda-s-tetravalent-dengue-vaccine-candidate-by-aedes-albopictus
#6
Elizabeth A Dietrich, Yee Tsuey Ong, Janae L Stovall, Hansi Dean, Claire Y-H Huang
Recombinant live-attenuated chimeric tetravalent dengue vaccine viruses, TDV-1, -2, -3, and -4, contain the premembrane and envelope genes of dengue virus serotypes 1-4 in the replicative background of the attenuated dengue virus type-2 (DENV-2) PDK-53 vaccine strain. Previous results have shown that these recombinant vaccine viruses demonstrate limited infection and dissemination in Aedes aegypti and are unlikely to be transmitted by the primary mosquito vector of DENVs. In this report, we expand this analysis by assessing vector competence of all four serotypes of the TDV virus in Aedes albopictus, the secondary mosquito vector of DENVs...
August 14, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28820501/interleukin-armed-chimeric-antigen-receptor-modified-t-cells-for-cancer-immunotherapy
#7
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/28819375/bone-marrow-derived-mesenchymal-stem-cells-involve-in-the-lymphangiogenesis-of-lung-cancer-and-jinfukang-inhibits-the-involvement-in-vivo
#8
Xian-Mei Zhou, Dan Wang, Hai-Lang He, Jie Tang, Jing Wu, Ling Xu, Jian-Xin Li
Lymphangiogenesis plays an important role in cancer metastasis. Bone marrow-derived mesenchymal stem cells (BMMSCs) migrate to the site of tumorigenesis and in turn promote the metastasis. However, whether BMMSCs involve in the lymphangiogenesis of lung cancer is unclear. Jinfukang has clinically been used for the treatment of non small cell lung cancer (NSCLC) in China. In this study, to investigate the involvement of BMMSCs in lymphangiogenesis in lung cancer, and evaluate the inhibitory effect of Jinfukang on the lymphangiogenesis, chimeric mice were prepared by transplanting bone marrow from green fluorescent protein (GFP) transgenic mice (C57BL/6-EGFP) into irradiated C57BL/6 mice...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#9
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but in some cases also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
August 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28818567/a-protein-chimera-including-pspa-in-fusion-with-potd-is-protective-against-invasive-pneumococcal-infection-and-reduces-nasopharyngeal-colonization-in-mice
#10
T R Converso, C Goulart, M Darrieux, L C C Leite
Despite the success of the available polysaccharide-based vaccines against Streptococcus pneumoniae in preventing invasive diseases, this bacterium remains a major cause of death in many parts of the world. New vaccine strategies are needed in order to increase protection. Thus, the utilization of fusion proteins is being investigated as an alternative to the current formulations. In the present work, we demonstrate that a chimeric protein, composed of PspA and PotD in fusion is able to maintain the protective characteristics of both parental proteins, providing protection against systemic infection while reducing nasal colonization...
August 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28818272/on-human-parthenogenesis
#11
Gabriel Jose de Carli, Tiago Campos Pereira
Spontaneous parthenogenetic and androgenetic events occur in humans, but they result in tumours: the ovarian teratoma and the hydatidiform mole, respectively. However, the observation of fetiform (ovarian) teratomas, the serependious identification of several chimeric human parthenotes and androgenotes in the last two decades, along with the creation of viable bi-maternal mice in the laboratory based on minor genetic interferences, raises the question of whether natural cases of clinically healthy human parthenotes have gone unnoticed to science...
September 2017: Medical Hypotheses
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
#12
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/28817100/modulatory-effects-of-exogenously-applied-polyamines-on-postharvest-physiology-antioxidant-system-and-shelf-life-of-fruits-a-review
#13
REVIEW
Sunil Sharma, Sunil Pareek, Narashans Alok Sagar, Daniel Valero, Maria Serrano
Polyamines (PAs) are natural compounds involved in many growth and developmental processes in plants, and, specifically in fruits, play a vital role regulating its development, ripening and senescence processes. Putrescine (PUT), spermine (SPE), and spermidine (SPD) are prominent PAs applied exogenously to extend shelf life of fruits. They also originate endogenously during developmental phases of horticultural crops and simultaneously affect the quality attributes and shelf life. Their anti-ethylene nature is being exploited to enhance the shelf life when exogenously applied on fruits...
August 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28816583/mammalian-cell-surface-display-for-monoclonal-antibody-based-facs-selection-of-viral-envelope-proteins
#14
Tim-Henrik Bruun, Veronika Grassmann, Benjamin Zimmer, Benedikt Asbach, David Peterhoff, Alexander Kliche, Ralf Wagner
The elicitation of broadly and efficiently neutralizing antibodies in humans by active immunization is still a major obstacle in the development of vaccines against pathogens such as the human immunodeficiency virus (HIV), influenza virus, hepatitis C virus or cytomegalovirus. Here, we describe a mammalian cell surface display and monoclonal antibody (mAb)-mediated panning technology that allows affinity-based selection of envelope (Env) variants from libraries. To this end, we established an experimental setup featuring: 1) single and site specific integration of Env to link genotype and phenotype, 2) inducible Env expression to avoid cytotoxicity effects, 3) translational coupling of Env and enhanced green fluorescent protein expression to normalize for Env protein levels, and 4) display on HEK cells to ensure native folding and mammalian glycosylation...
August 17, 2017: MAbs
https://www.readbyqxmd.com/read/28814300/increasing-on-target-cleavage-efficiency-for-crispr-cas9-induced-large-fragment-deletion-in-myxococcus-xanthus
#15
Ying-Jie Yang, Ye Wang, Zhi-Feng Li, Ya Gong, Peng Zhang, Wen-Chao Hu, Duo-Hong Sheng, Yue-Zhong Li
BACKGROUND: The CRISPR/Cas9 system is a powerful tool for genome editing, in which the sgRNA binds and guides the Cas9 protein for the sequence-specific cleavage. The protocol is employable in different organisms, but is often limited by cell damage due to the endonuclease activity of the introduced Cas9 and the potential off-target DNA cleavage from incorrect guide by the 20 nt spacer. RESULTS: In this study, after resolving some critical limits, we have established an efficient CRISPR/Cas9 system for the deletion of large genome fragments related to the biosynthesis of secondary metabolites in Myxococcus xanthus cells...
August 16, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28811975/chemotherapeutic-agent-mediated-elimination-of-myeloid-derived-suppressor-cells
#16
REVIEW
Zibing Wang, Brian Till, Quanli Gao
Immunotherapy has shown great promise in the fight against cancer, as evidenced by the clinical efficacy of chimeric antigen receptor T cells in hematologic malignancies and checkpoint blockade in certain solid tumors. However, a considerable number of patients fail to respond to these therapies. Induction of myeloid-derived suppressor cells (MDSCs) by growing tumors has been shown to be one important factor limiting the efficacy of cancer immunotherapy. Recently, several chemotherapeutic agents used in conventional cancer chemotherapy have been found to reduce MDSC numbers in tumor tissues as well as in the peripheral lymphoid organs, and combining these agents with immunotherapy improved survival of tumor-bearing hosts...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811604/multimerization-is-required-for-antigen-binding-activity-of-an-engineered-igm-igg-chimeric-antibody-recognizing-a-skin-related-antigen
#17
Kwesi Teye, Koji Hashimoto, Sanae Numata, Kunihiro Ohta, Marek Haftek, Takashi Hashimoto
Monoclonal antibodies offer great tools for research. We encountered a potentially useful mouse IgM monoclonal antibody whose antigen is expressed in normal skin but lost in human skin cancer. Because IgM is difficult to work with and the antigen was unknown, we decided to convert the IgM (µ) to IgG (γ) version. After cDNA for the antibody was obtained by RACE PCR, we made a series of molecules with different combinations of IgM and IgG domains. Whereas VH-Cµ1-Cµ2-Cγ3 and VH-Cµ1-Cµ2-Hinge-Cγ2-Cγ3 functionally bound to the antigen, VH-Cγ1-Hinge-Cγ2-Cγ3, VH-Cµ1-Hinge-Cγ2-Cγ3, and VH-Cµ1-Cµ2-Cγ2-Cγ3 did not...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811492/interferon-alpha-treatment-rapidly-clears-hepatitis-e-virus-infection-in-humanized-mice
#18
Martijn D B van de Garde, Suzan D Pas, Gertine W van Oord, Lucio Gama, Youkyung Choi, Robert A de Man, Andre Boonstra, Thomas Vanwolleghem
Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810809/optimization-of-human-nk-cell-manufacturing-fully-automated-separation-improved-i-ex-vivo-i-expansion-using-il-21-with-autologous-feeder-cells-and-generation-of-anti-cd123-car-expressing-effector-cells
#19
Stephan Klöß, Olaf Oberschmidt, Michael Morgan, Julia Dahlke, Lubomir Arseniev, Volker Huppert, Markus Granzin, Tanja Gardlowski, Nadine Matthies, Stefanie Soltenborn, Axel Schambach, Ulrike Koehl
BACKGROUND AND AIMS: The administration of ex-vivo expanded Natural killer (NK) cells as potential antitumor effector cells appears to be suitable for effector cell-based immunotherapies in high-risk cancer patients. However, the GMP-conform manufacturing of clinical-grade NK cells at sufficiently high numbers represent a great challenge. Therefore, we improved and optimized previous expansion protocols for those effector cells through the use of newly developed culture medium, IL-21 and autologous feeder cells...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28810803/driving-cars-on-the-highway-to-solid-cancer-some-considerations-on-the-adoptive-therapy-with-car-t-cells
#20
Hinrich Abken
Adoptive therapy with chimeric antigen receptor (CAR) redirected T cells achieved lasting remissions in hematologic malignancies even in terminal stages of the disease; exploring CAR T cell therapy in the treatment of solid tumors has just begun, balancing efficacy versus toxicity in early phase trials. In contrast to leukemia/lymphoma, solid tumors display a tremendously variable biology demanding different strategies to make a T cell attack successful in the long-term. We summarize current developments, discuss the hurdles and consider some modifications to improve the CAR T cell therapy in the treatment of solid tumors...
August 16, 2017: Human Gene Therapy
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