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https://www.readbyqxmd.com/read/28938609/pegylated-arginine-deiminase-can-modulate-tumor-immune-microenvironment-by-affecting-immune-checkpoint-expression-decreasing-regulatory-t-cell-accumulation-and-inducing-tumor-t-cell-infiltration
#1
Elena Brin, Katherine Wu, Hsin-Tze Lu, Yudou He, Zhaoming Dai, Wei He
PEGylated arginine deiminase (ADI-PEG 20) is being investigated in clinical studies in arginine auxotrophic cancers and is well-tolerated. The anti-tumor properties of ADI-PEG 20 have been extensively investigated - ADI-PEG 20 inhibits the growth of auxotrophic cancers in vitro and in vivo - however, its impact on immune cells is largely unknown. Here we report the potential impact of ADI-PEG 20 on the tumor immune microenvironment. ADI-PEG 20 induced immunosuppressive programmed death-ligand 1 expression on some cancer cells in vitro, but the magnitude of the increase was cell line dependent and in most relatively small...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938559/doxorubicin-loaded-platelets-conjugated-with-anti-cd22-mabs-a-novel-targeted-delivery-system-for-lymphoma-treatment-with-cardiopulmonary-avoidance
#2
Peipei Xu, Huaqin Zuo, Rongfu Zhou, Fan Wang, Xu Liu, Jian Ouyang, Bing Chen
B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938115/a-human-bi-specific-antibody-against-zika-virus-with-high-therapeutic-potential
#3
Jiaqi Wang, Marco Bardelli, Diego A Espinosa, Mattia Pedotti, Thiam-Seng Ng, Siro Bianchi, Luca Simonelli, Elisa X Y Lim, Mathilde Foglierini, Fabrizia Zatta, Stefano Jaconi, Martina Beltramello, Elisabetta Cameroni, Guntur Fibriansah, Jian Shi, Taylor Barca, Isabel Pagani, Alicia Rubio, Vania Broccoli, Elisa Vicenzi, Victoria Graham, Steven Pullan, Stuart Dowall, Roger Hewson, Simon Jurt, Oliver Zerbe, Karin Stettler, Antonio Lanzavecchia, Federica Sallusto, Andrea Cavalli, Eva Harris, Shee-Mei Lok, Luca Varani, Davide Corti
Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28937210/multivariate-analysis-of-2d-1-h-13-c-methyl-nmr-spectra-of-monoclonal-antibody-therapeutics-to-facilitate-assessment-of-higher-order-structure
#4
Luke Arbogast, Frank Delaglio, John E Schiel, John P Marino
Two-dimensional (2D) 1H-13C methyl NMR provides a powerful tool to probe the higher order structure (HOS) of monoclonal antibodies (mAbs), since spectra can readily be acquired on intact mAbs at natural isotopic abundance, and small changes in chemical environment and structure give rise to observable changes in corresponding spectra, which can be interpreted at atomic resolution. This makes it possible to apply 2D NMR spectral fingerprinting approaches directly to drug products in order to systematically characterize structure and excipient effects...
September 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28935894/strain-dependent-neutralization-reveals-antigenic-variation-of-human-parechovirus-3
#5
Eveliina Karelehto, Sabine van der Sanden, James A Geraets, Aušra Domanska, Lonneke van der Linden, Dionne Hoogendoorn, Gerrit Koen, Hetty van Eijk, Shabih Shakeel, Tim Beaumont, Menno de Jong, Dasja Pajkrt, Sarah J Butcher, Katja C Wolthers
Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide. However, the observed seropositivity rates for HPeV3 neutralizing antibodies (nAbs) vary from high in Japan to low in the Netherlands and Finland. To study if this can be explained by technical differences or antigenic diversity among HPeV3 strains included in the serological studies, we determined the neutralizing activity of Japanese and Dutch intravenous immunoglobulin batches (IVIG), a rabbit HPeV3 hyperimmune polyclonal serum, and a human HPeV3-specific monoclonal antibody (mAb) AT12-015, against the HPeV3 A308/99 prototype strain and clinical isolates from Japan, the Netherlands and Australia, collected between 1989 and 2015...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28933731/a-novel-fluoroimmunoassay-for-detecting-ruscogenin-with-monoclonal-antibodies-conjugated-with-cdse-zns-quantum-dots
#6
Hongwei Zhang, Tao Xu, Lan Gao, Xiufeng Liu, Jihua Liu, Boyang Yu
Ruscogenin (RUS) is a steroidal sapogenin found in Ruscus aculeatus and Ophiopogon japonicus with several pharmacological activities. In the work reported herein, a novel method termed competitive fluorescence-linked immunosorbent assay (cFLISA) based on monoclonal antibodies (mAbs) coupled with quantum dots (QDs) was developed for the quick and sensitive determination of RUS in biological samples. The mAbs against RUS were conjugated with CdSe/ZnS QDs by the crossing-linking reagents and an indirect cFLISA method was developed...
July 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28933689/galk-based-suicide-vector-mediated-allelic-exchange-in-mycobacterium-abscessus
#7
Stacy A Gregoire, Joel Byam, Martin S Pavelka
Mycobacterium abscessus is a fast-growing environmental organism and an important emerging pathogen. It is highly resistant to many antibiotics and undergoes a smooth to rough colony morphology change that appears to be important for pathogenesis. Smooth environmental strains have a glycopeptidolipid (GPL) on the surface, while certain types of clinical strains are often rough and lack this GPL, due to mutations in biosynthetic genes or the mmpL4b transporter gene. We report here the development and evaluation of an allelic exchange system for unmarked alleles in M...
September 21, 2017: Microbiology
https://www.readbyqxmd.com/read/28933642/epitope-characterization-of-anti-jam-a-antibodies-using-orthogonal-mass-spectrometry-and-surface-plasmon-resonance-approaches
#8
Guillaume Terral, Thierry Champion, François Debaene, Olivier Colas, Maxime Bourguet, Elsa Wagner-Rousset, Nathalie Corvaia, Alain Beck, Sarah Cianferani
Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein expressed by endothelial and epithelial cells and associated with cancer progression. We present here the extensive characterization of immune complexes involving JAM-A antigen and three monoclonal antibodies (mAbs), including hz6F4-2, a humanized version of anti-tumoral 6F4 mAb identified by a functional and proteomic approach in our laboratory. A specific workflow that combines orthogonal approaches has been designed to determine binding stoichiometries along with JAM-A epitope mapping determination at high resolution for these three mAbs...
September 21, 2017: MAbs
https://www.readbyqxmd.com/read/28931897/identification-and-characterization-of-a-novel-sso7d-scaffold-based-binder-against-notch1
#9
Tenzin Gocha, Balaji M Rao, Ramanuj DasGupta
Notch signaling has important functions in regulating cell growth and development, misregulation of which has been implicated in various cancers. Monoclonal antibodies (mAbs) targeting Notch protein activity have already moved into clinical trials. However due to the limitations associated with cost and productivity of mAbs, there has been a surge in the development of complementary approaches that are based on non-antibody scaffolds. Non-antibody scaffolds are small proteins that are stable and can be engineered to develop high-affinity binders against specific targets of interest...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931787/heparin-induces-the-mobilization-of-heart-derived-multipotent-mesoangioblasts-during-cardiac-surgery-with-cardiopulmonary-bypass-or-cardiac-catheterization
#10
Yoshihiro Hata, Masayoshi Iwasaki, Keisuke Fujitaka, Haengnam Park, Daisuke Sato, Chiharu Enoki, Naoki Minato, Keita Horitani, Miyuki Nakano, Hiroshi Kishimoto, Kensaku Wada, Masamichi Koyanagi, Yasushi Adachi, Yoshihiro Yamamoto, Andreas M Zeiher, Stefanie Dimmeler, Ichiro Shiojima
BACKGROUND: We previously identified circulating mesoangioblasts (cMABs), a subset of mesenchymal stem cells that express cardiac mesodermal markers, in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). We also found that hepatocyte growth factor (HGF) is upregulated during cardiac surgery with CPB in humans, and induces MAB-like cell mobilization in rodents. These results strongly suggest that heparin induced MAB mobilization via HGF upregulation. Here, we tested this hypothesis in patients undergoing cardiac surgery or cardiac catheterization...
September 21, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28931235/monoclonal-antibody-protects-against-acinetobacter-baumannii-infection-by-enhancing-bacterial-clearance-and-evading-sepsis
#11
Travis B Nielsen, Paul Pantapalangkoor, Brian M Luna, Kevin W Bruhn, Jun Yan, Ken Dekitani, Sarah Hsieh, Brandon Yeshoua, Bryan Pascual, Evgeny Vinogradov, Kristine M Hujer, T Nicholas Domitrovic, Robert A Bonomo, Thomas A Russo, Magda Lesczcyniecka, Thomas Schneider, Brad Spellberg
Background: Extremely drug-resistant (XDR) Acinetobacter baumannii is one of the most commonly encountered, highly resistant pathogens requiring novel therapeutic interventions. Methods: We developed C8, a monoclonal antibody (mAb), by immunizing mice with sublethal inocula of a hypervirulent XDR clinical isolate. Results: C8 targets capsular carbohydrate on the bacterial surface, enhancing opsonophagocytosis. Treating with a single dose of C8 as low as 0...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28928164/immunopet-of-malignant-and-normal-b-cells-with%C3%A2-89-zr-and%C3%A2-124-i-labeled-obinutuzumab-antibody-fragments-reveals-differential-cd20-internalization-in-vivo
#12
Kirstin A Zettlitz, Richard Tavare, Scott M Knowles, Kristopher K Steward, John M Timmerman, Anna M Wu
PURPOSE: The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20. EXPERIMENTAL DESIGN: Anti-CD20 cys-diabody (cDb) and cys-minibody (cMb) based on rituximab (Rx) and obinutuzumab (GA101) were radioiodinated and used for immunoPET imaging of a murine lymphoma model...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928120/creation-of-a-claudin-2-binder-and-its-tight-junction-modulating-activity-in-a-human-intestinal-model
#13
Mutsumi Takigawa, Manami Iida, Shotaro Nagase, Hidehiko Suzuki, Akihiro Watari, Minoru Tada, Yoshiaki Okada, Takefumi Doi, Masayoshi Fukasawa, Kiyohito Yagi, Jun Kunisawa, Masuo Kondoh
Disruption of the gastrointestinal epithelial barrier is a hallmark of chronic inflammatory bowel diseases (IBDs). The transmembrane protein claudin 2 (CLDN2) is a component of epithelial tight junctions (TJs). In the intestines of patients with IBDs, the expression of the pore-forming TJ protein CLDN2 is upregulated. Although CLDN2 is involved in these leaky barriers, whether it can be a target to enhance TJ integrity is unknown because a CLDN2-specific inhibitor has not been developed. Here, we used DNA immunization to generate a monoclonal antibody (mAb) that recognized an extracellular loop of CLDN2...
September 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28926977/mouse-monoclonal-antibodies-generated-from-full-length-human-cereblon-detection-of-cereblon-protein-in-patients-with-multiple-myeloma
#14
Xiubao Chang, Qinqin Xu, Yuexian Hou, Cynthia Li, Ye Xu, A Keith Stewart
Immunomodulatory drugs (IMiDs) are profoundly active compounds in the treatment of patients with multiple myeloma (MM). However, despite the fact that treatment with IMiDs has dramatically improved survival for patients with MM, the majority of MM patients develop IMiDs resistance over time. We have found that expression of functional cereblon is required for IMiDs' action. In addition, it has been reported that cells expressing high levels of cereblon are resistant to proteasome inhibitor, implying that patients with high levels of cereblon should be resistant to proteasome inhibitor...
September 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926962/anti-nkg2d-mab-a-new-treatment-for-crohn-s-disease
#15
REVIEW
Kasper Vadstrup, Flemming Bendtsen
Crohn's disease (CD) and ulcerative colitis (UC) are immunologically-mediated, debilitating conditions resulting from destructive inflammation of the gastrointestinal tract. The pathogenesis of IBD is incompletely understood, but is considered to be the result of an abnormal immune response with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56⁺ T, and CD8⁺ T cells...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926954/evidence-for-complex-formation-of-the-bacillus-cereus-haemolysin-bl-components-in-solution
#16
Franziska Tausch, Richard Dietrich, Kristina Schauer, Robert Janowski, Dierk Niessing, Erwin Märtlbauer, Nadja Jessberger
Haemolysin BL is an important virulence factor regarding the diarrheal type of food poisoning caused by Bacillus cereus. However, the pathogenic importance of this three-component enterotoxin is difficult to access, as nearly all natural B. cereus culture supernatants additionally contain the highly cytotoxic Nhe, the second three-component toxin involved in the aetiology of B. cereus-induced food-borne diseases. To better address the toxic properties of the Hbl complex, a system for overexpression and purification of functional, cytotoxic, recombinant (r)Hbl components L₂, L₁ and B from E...
September 16, 2017: Toxins
https://www.readbyqxmd.com/read/28926943/monoclonal-antibodies-in-preclinical-eae-models-of-multiple-sclerosis-a-systematic-review
#17
REVIEW
Katja Schmitz, Gerd Geisslinger, Irmgard Tegeder
Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28923920/microrna-dysregulation-to-identify-therapeutic-target-combinations-for-chronic-lymphocytic-leukemia
#18
Laura Z Rassenti, Veronica Balatti, Emanuela M Ghia, Alexey Palamarchuk, Luisa Tomasello, Paolo Fadda, Yuri Pekarsky, George F Widhopf, Thomas J Kipps, Carlo M Croce
Loss of miR-15/16 is the most common genetic lesion in chronic lymphocytic leukemia (CLL), promoting overexpression of BCL2, which factors in leukemia pathogenesis. Indeed, an inhibitor of Bcl2, venetoclcax, is highly active in the treatment of patients with CLL. However, single-agent venetoclcax fails to eradicate minimal residual disease in most patients. Accordingly, we were interested in other genes that may be regulated by miR-15/16, which may target other drivers in CLL. We found that miR-15/16 targets ROR1, which encodes an onco-embryonic surface protein expressed on the CLL cells of over 90% of patients, but not on virtually all normal postpartum tissues...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923914/new-ultrasound-techniques-promise-further-advances-in-aki-and-ckd
#19
REVIEW
Travis D Hull, Anupam Agarwal, Kenneth Hoyt
AKI and CKD are important clinical problems because they affect many patients and the associated diagnostic and treatment paradigms are imperfect. Ultrasound is a cost-effective, noninvasive, and simple imaging modality that offers a multitude of means to improve the diagnosis, monitoring, and treatment of both AKI and CKD, especially considering recent advances in this technique. Ultrasound alone can attenuate AKI and prevent CKD by stimulating the splenic cholinergic anti-inflammatory pathway. Additionally, microbubble contrast agents are improving the sensitivity and specificity of ultrasound for diagnosing kidney disease, especially when these agents are conjugated to ligand-specific mAbs or peptides, which make the dynamic assessment of disease progression and response to treatment possible...
September 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28923838/syngeneic-mouse-models-of-oral-cancer-are-effectively-targeted-by-anti-cd44-based-nir-pit
#20
Tadanobu Nagaya, Yuko Nakamura, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Peter L Choyke, Clint Alen, Hisataka Kobayashi
Oral cavity squamous cell carcinoma (OSCC) is considered one of the most aggressive subtypes of cancer. Anti-CD44 monoclonal antibodies (mAbs) are a potential therapy against CD44 expressing OSCC, however, to date the therapeutic effects have been disappointing. Here, a new cancer treatment is described, near-infrared photoimmunotherapy (NIR-PIT), that uses anti-CD44 mAbs conjugated to the photoabsorber, IR700DX. This conjugate is injected into mice harboring one of three CD44 expressing syngeneic murine oral cancer cell (MOC) lines, MOC1 (immunogenic), MOC2 mKate2 (moderately immunogenic), and MOC2-luc (poorly immunogenic)...
September 18, 2017: Molecular Cancer Research: MCR
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