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https://www.readbyqxmd.com/read/29908151/vaccination-with-a-cd4-and-cd8-t-cell-epitopes-based-recombinant-chimeric-protein-derived-from-leishmania-infantum-proteins-confers-protective-immunity-against-visceral-leishmaniasis
#1
Daniel S Dias, Patrícia A F Ribeiro, Vívian T Martins, Daniela P Lage, Lourena E Costa, Miguel A Chávez-Fumagalli, Fernanda F Ramos, Thaís T O Santos, Fernanda Ludolf, Jamil S Oliveira, Tiago A O Mendes, Eduardo S Silva, Alexsandro S Galdino, Mariana C Duarte, Bruno M Roatt, Daniel Menezes-Souza, Antonio L Teixeira, Eduardo A F Coelho
Vaccination seems to be the best approach to control visceral leishmaniasis (VL). Resistance against infection is based on the development of a Th1 immune response characterized by the production of interferons-γ (IFN-γ), interleukin-12 (IL-12), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α), among others. A number of antigens have been tested as potential targets against the disease; few of them are able to stimulate human immune cells. In the present study, 1 prediction of MHC class I and II molecules-specific epitopes in the amino acid sequences of 3 Leishmania proteins: 1 hypothetical, prohibitin, and small glutamine-rich tetratricopeptide repeat-containing proteins, was performed using bioinformatics tools, and a T-cell epitopes-based recombinant chimeric protein was constructed, synthetized and purified to be evaluated in invitro and in vivo experiments...
May 22, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29907459/nlrc5-deficiency-protects-against-acute-kidney-injury-in-mice-by-mediating-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-signaling
#2
Quanxin Li, Ziying Wang, Yan Zhang, Jiaqing Zhu, Liang Li, Xiaojie Wang, Xiaoyang Cui, Yu Sun, Wei Tang, Chengjiang Gao, Chunhong Ma, Fan Yi
There is significant progress in understanding the structure and function of NLRC5, a member of the nucleotide oligomerization domain-like receptor family. However, in the context of MHC class I gene expression, the functions of NLRC5 in innate and adaptive immune responses beyond the regulation of MHC class I genes remain controversial and unresolved. In particular, the role of NLRC5 in the kidney is unknown. NLRC5 was significantly upregulated in the kidney from mice with renal ischemia/reperfusion injury...
June 12, 2018: Kidney International
https://www.readbyqxmd.com/read/29907163/cytokine-release-syndrome
#3
REVIEW
Alexander Shimabukuro-Vornhagen, Philipp Gödel, Marion Subklewe, Hans Joachim Stemmler, Hans Anton Schlößer, Max Schlaak, Matthias Kochanek, Boris Böll, Michael S von Bergwelt-Baildon
During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS)...
June 15, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29906450/inactivation-of-cdk12-delineates-a-distinct-immunogenic-class-of-advanced-prostate-cancer
#4
Yi-Mi Wu, Marcin Cieślik, Robert J Lonigro, Pankaj Vats, Melissa A Reimers, Xuhong Cao, Yu Ning, Lisha Wang, Lakshmi P Kunju, Navonil de Sarkar, Elisabeth I Heath, Jonathan Chou, Felix Y Feng, Peter S Nelson, Johann S de Bono, Weiping Zou, Bruce Montgomery, Ajjai Alva, Dan R Robinson, Arul M Chinnaiyan
Using integrative genomic analysis of 360 metastatic castration-resistant prostate cancer (mCRPC) samples, we identified a novel subtype of prostate cancer typified by biallelic loss of CDK12 that is mutually exclusive with tumors driven by DNA repair deficiency, ETS fusions, and SPOP mutations. CDK12 loss is enriched in mCRPC relative to clinically localized disease and characterized by focal tandem duplications (FTDs) that lead to increased gene fusions and marked differential gene expression. FTDs associated with CDK12 loss result in highly recurrent gains at loci of genes involved in the cell cycle and DNA replication...
June 14, 2018: Cell
https://www.readbyqxmd.com/read/29906413/a-snap-25-cleaving-chimera-of-botulinum-neurotoxin-a-and-e-prevents-tnf%C3%AE-induced-elevation-of-the-activities-of-native-trp-channels-on-early-postnatal-rat-dorsal-root-ganglion-neurons
#5
Marc Nugent, Yamil R Yusef, Jianghui Meng, Jiafu Wang, J Oliver Dolly
Transient receptor potential (TRP) vallinoid 1 (TRPV1) and ankyrin 1 (TRPA1) are two transducing channels expressed on peripheral sensory nerves involved in pain sensation. Upregulation of their expression, stimulated by inflammatory cytokines and growth factors in animal pain models, correlate with the induction of nociceptive hyper-sensitivity. Herein, we firstly demonstrate by immuno-cytochemical labelling that TNFα augments the surface content of these channels on rat cultured dorsal root ganglion (DRG) neurons which, in turn, enhances the electrophysiological and functional responses of the latter to their specific agonists...
June 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29906396/synthesis-and-evaluation-of-n-phenyl-3-sulfamoyl-benzamide-derivatives-as-capsid-assembly-modulators-inhibiting-hepatitis-b-virus-hbv
#6
Koen Vandyck, Geert Rombouts, Bart Stoops, Abdellah Tahri, Ann Vos, Wim Verschueren, Yiming Wu, Jingmei Yang, Fuliang Hou, Bing Huang, Karen Vergauwen, Pascale Dehertogh, Jan-Martin Berke, Pierre Jean Marie Bernard Raboisson
Small molecule induced Hepatitis B virus (HBV) capsid assembly modulation is considered an attractive approach for new antiviral therapies against HBV. Here we describe efforts towards the discovery of a HBV capsid assembly modulator in a hit-to-lead optimization, resulting in JNJ-632, a tool compound used to further profile the mode of action. Administration of JNJ-632 (54) in HBV genotype D infected chimeric mice, resulted in a 2.77 log reduction of the HBV DNA viral load.
June 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29906032/microcephaly-and-arbovirus
#7
Luis Del Carpio-Orantes, María del Carmen González-Clemente
In this paper the relationship between the incidence of microcephaly and various arboviruses in current boom is exposed. It stands out that in the infection by the dengue virus, there have been no cases of microcephaly, however in the case series of chikungunya infection, incidence of cases with this affectation was reported, highlighting a cohort called CHIMERE; also the highest incidence of microcephaly associated with the mentioned Zika virus, which has been widely studied. All this, due to the neurotropism of these arboviruses...
March 2018: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/29904678/cpc-etc1-chimeric-protein-localization-data-in-arabidopsis-root-epidermis
#8
R Tominaga-Wada, T Wada
Intercellular movement of transcription factor proteins is essential for plant development. The R3 type MYB transcription factor protein, CAPRICE (CPC), moves from non-hair cells to root-hair cells where it promotes root hair formation in Arabidopsis root epidermis. In contrast, the CPC homolog of ENHANCER OF TRY AND CPC1 (ETC1) cannot move in root epidermal cells. In this work, we present protein localization data of CPC-ETC1 chimeric proteins. Localization of CPC-ETC1-GFP fusion proteins of chimera1 and chimera2 transgenic plants was observed using confocal laser scanning microscope...
June 2018: Data in Brief
https://www.readbyqxmd.com/read/29904021/overcoming-resistance-of-human-non-hodgkin-s-lymphoma-to-cd19-car-ctl-therapy-by-celecoxib-and-histone-deacetylase-inhibitors
#9
Antoni Xavier Torres-Collado, Ali R Jazirehi
Patients with B-cell non-Hodgkin’s lymphoma (B-NHL) who fail to respond to first-line treatment regimens or develop resistance, exhibit poor prognosis. This signifies the need to develop alternative treatment strategies. CD19-chimeric antigen receptor (CAR) T cell-redirected immunotherapy is an attractive and novel option, which has shown encouraging outcomes in phase I clinical trials of relapsed/refractory NHL. However, the underlying mechanisms of, and approaches to overcome, acquired anti-CD19CAR CD8⁺ T cells (CTL)-resistance in NHL remain elusive...
June 14, 2018: Cancers
https://www.readbyqxmd.com/read/29903928/antibody-with-infinite-affinity-for-in-vivo-tracking-of-genetically-engineered-lymphocytes
#10
Simone Krebs, Afruja Ahad, Lukas Carter, Justin Eyquem, Christian Brand, Meghan Bell, Vladimir Ponomarev, Thomas Reiner, Claude F Meares, Stephen Gottschalk, Michel Sadelain, Steven M Larson, Wolfgang Andreas Weber
There remains an urgent need for the non-invasive tracking of transfused chimeric antigen receptor (CAR) T cells to determine their biodistribution, viability, expansion, and anti-tumor functionality. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) antibody reporter 1 (DAbR1) comprises a single-chain fragment of the anti-lanthanoid-DOTA antibody 2D12.5/G54C fused to the human CD4-transmembrane domain and binds irreversibly to lanthanoid-(S)-2-(4-acrylamidobenzyl)-DOTA (AABD). The aim of this study was to investigate whether DAbR1 can be expressed on lymphocytes and used as a reporter gene as well as a suicide gene for therapy of immune-related adverse effects...
June 14, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29903916/insulin-like-growth-factor-1-receptor-stabilizes-the-etv6-ntrk3-chimeric-oncoprotein-by-blocking-its-kpc1-rnf123-mediated-proteasomal-degradation
#11
Cristina E Tognon, Bo Rafn, Naniye Malli Cetinbas, Takumi Kamura, Genny Trigo, Barak Rotblat, Fumihiko Okumura, Masaki Matsumoto, Christine Chow, Monika Davare, Michael Pollak, Thibault Mayor, Poul H Sorensen
Many oncogenes, including chimeric oncoproteins, require insulin-like growth factor 1 receptor (IGF1R) for promoting cell transformation. The ETS variant 6 (ETV6)-neurotrophic receptor tyrosine kinase 3 (NTRK3) (EN) chimeric tyrosine kinase is expressed in mesenchymal, epithelial, and hematopoietic cancers and requires the IGF1R axis for transformation. However, current models of IGF1R-mediated EN activation are lacking mechanistic detail. We demonstrate here that IGF-mediated IGF1R stimulation enhances EN tyrosine phosphorylation and that blocking IGF1R activity or decreasing protein levels of the adaptor protein insulin receptor substrate 1/2 (IRS1/2) results in rapid EN degradation...
June 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29903894/novel-approaches-to-acute-myeloid-leukemia-immunotherapy
#12
Ofrat Beyar-Katz, Saar Gill
Acute myeloid leukemia (AML) is a rapidly progressive, poor-prognosis malignancy arising from hematopoietic stem/progenitor cells. The long history of successful use of allogeneic hematopoietic cell transplantation (alloHCT) in AML indicates that this disease is immunoresponsive, leading to optimism that novel immunotherapies such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors will generate meaningful disease control. However, emerging data on the immunoevasive tactics employed by AML blasts at diagnosis and at relapse indicate that optimism must be tempered by an understanding of this essential paradox...
June 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29902792/xy-sry-positive-ovarian-disorder-of-sex-development-in-cattle
#13
Lisa De Lorenzi, Silvana Arrighi, Elena Rossi, Pierangela Grignani, Carlo Previderè, Stefania Bonacina, Fausto Cremonesi, Pietro Parma
In mammals, the sex of the embryo depends on the SRY gene. In the presence of at least one intact and functional copy of this genetic factor (XY embryo) undifferentiated gonads will develop as testicles that subsequently determine the male phenotype. When this factor is not present, i.e., in subjects with 2 X chromosomes, an alternative pathway induces the development of ovaries, hence a female phenotype. In this case study, we describe a female cattle affected by a disorder of sex development (DSD). The subject, despite having a chromosomal XY constitution, did not develop testicles but ovaries, although they were underdeveloped...
June 13, 2018: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/29901248/chimeric-xna-an-unconventional-design-for-orthogonal-informational-systems
#14
Tim Efthymiou, Jesse Gavette, Matthias Stoop, Francesco De Riccardis, Mathy Froeyen, Piet Herdewyn, Ramanarayanan Krishnamurthy
The paradigm of homogenous-sugar-backbone of RNA and DNA has reliably guided the construction of many functional and useful Xeno Nucleic Acid (XNA) systems to date. Deviations from this monotonous and canonical design, in many cases, results in oligonucleotide systems which lack base-pairing with themselves, or with RNA or DNA. Here we show that nucleotides of two such compromised XNA systems can be combined with RNA and DNA in specific patterns to produce chimeric-backbone oligonucleotides, which in certain cases demonstrate base-pairing properties comparable to -or stronger than- canonical systems, while also altering the conventional Watson-Crick pairing behavior...
June 14, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29900058/optimized-dendritic-cell-vaccination-induces-potent-cd8-t-cell-responses-and-anti-tumor-effects-in-transgenic-mouse-melanoma-models
#15
Mareike Grees, Adi Sharbi-Yunger, Christos Evangelou, Daniel Baumann, Gal Cafri, Esther Tzehoval, Stefan B Eichmüller, Rienk Offringa, Jochen Utikal, Lea Eisenbach, Viktor Umansky
Despite melanoma immunogenicity and remarkable therapeutic effects of negative immune checkpoint inhibitors, a significant fraction of patients does not respond to current treatments. This could be due to limitations in tumor immunogenicity and profound immunosuppression in the melanoma microenvironment. Moreover, insufficient tumor antigen processing and presentation by dendritic cells (DC) may hamper the development of tumor-specific T cells. Using two genetically engineered mouse melanoma models ( RET and BRAFV600E transgenic mice), in which checkpoint inhibitor therapy alone is not efficacious, we performed proof-of-concept studies with an improved, multivalent DC vaccination strategy based on our recently developed genetic mRNA cancer vaccines...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29900044/cd133-directed-car-t-cells-for-advanced-metastasis-malignancies-a-phase-i-trial
#16
Yao Wang, Meixia Chen, Zhiqiang Wu, Chuan Tong, Hanren Dai, Yelei Guo, Yang Liu, Jianhua Huang, Haiyan Lv, Can Luo, Kai-Chao Feng, Qing-Ming Yang, Xiao-Lei Li, Weidong Han
Expressed by cancer stem cells of various epithelial cell origins, CD133 is an attractive therapeutic target for cancers. Autologous chimeric antigen receptor-modified T-cell directed CD133 (CART-133) was first tested in this trial. The anti-tumor specificity and the postulated toxicities of CART-133 were first assessed. Then, we conducted a phase I clinical study in which patients with advanced and CD133-positive tumors received CART-133 cell-infusion. We enrolled 23 patients (14 with hepatocellular carcinoma [HCC], 7 with pancreatic carcinomas, and 2 with colorectal carcinomas)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29899889/acute-myeloid-leukemia-chimeric-antigen-receptor-t-cell-immunotherapy-how-far-up-the-road-have-we-traveled
#17
REVIEW
Sarah K Tasian
Chemotherapy resistance and relapse remain significant sources of mortality for children and adults with acute myeloid leukemia (AML). Further intensification of conventional cytotoxic chemotherapy is likely not feasible due to the severity of acute and long-term side effects upon normal tissues commonly induced by these drugs. Successful development and implementation of new precision medicine treatment approaches for patients with AML, which may improve leukemia remission and diminish toxicity, is thus a major priority...
June 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29899861/deregulation-of-calcium-homeostasis-in-bcr-abl-dependent-chronic-myeloid-leukemia
#18
Hélène Cabanas, Thomas Harnois, Christophe Magaud, Laëtitia Cousin, Bruno Constantin, Nicolas Bourmeyster, Nadine Déliot
Background: Chronic myeloid leukemia (CML) results from hematopoietic stem cell transformation by the bcr-abl chimeric oncogene, encoding a 210 kDa protein with constitutive tyrosine kinase activity. In spite of the efficiency of tyrosine kinase inhibitors (TKI; Imatinib), other strategies are explored to eliminate CML leukemia stem cells, such as calcium pathways. Results: In this work, we showed that Store-Operated Calcium Entry (SOCE) and thrombin induced calcium influx were decreased in Bcr-Abl expressing 32d cells (32d-p210)...
May 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899820/pre-clinical-validation-of-b-cell-maturation-antigen-bcma-as-a-target-for-t-cell-immunotherapy-of-multiple-myeloma
#19
De-Xiu Bu, Reshma Singh, Eugene E Choi, Marco Ruella, Selene Nunez-Cruz, Keith G Mansfield, Paul Bennett, Nathanial Barton, Qilong Wu, Jiquan Zhang, Yongqiang Wang, Lai Wei, Shawn Cogan, Tucker Ezell, Shree Joshi, Kellie J Latimer, Brian Granda, William R Tschantz, Regina M Young, Heather A Huet, Celeste J Richardson, Michael C Milone
Multiple myeloma has a continued need for more effective and durable therapies. B cell maturation antigen (BCMA), a plasma cell surface antigen and member of the tumor necrosis factor (TNF) receptor superfamily, is an attractive target for immunotherapy of multiple myeloma due to its high prevalence on malignant plasma cells. The current work details the pre-clinical evaluation of BCMA expression and development of a chimeric antigen receptor (CAR) targeting this antigen using a fully human single chain variable fragment (scFv)...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899740/gmp-grade-manufacturing-of-t-cells-engineered-to-express-a-defined-%C3%AE-%C3%AE-tcr
#20
Trudy Straetemans, Guido J J Kierkels, Ruud Doorn, Koen Jansen, Sabine Heijhuurs, Joao M Dos Santos, Anna D D van Muyden, Henri Vie, Béatrice Clemenceau, Reinier Raymakers, Moniek de Witte, Zsolt Sebestyén, Jürgen Kuball
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have developed the concept of T cells engineered to express a defined γδT cell receptor (TEGs). This next generation of chimeric antigen receptor engineered T (CAR-T) cells not only allows for targeting of hematological but also of solid tumors and, therefore, overcomes major limitations of many CAR-T and γδT cell strategies...
2018: Frontiers in Immunology
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