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https://www.readbyqxmd.com/read/28640663/glycosylation-profile-and-biological-activity-of-remicade%C3%A2-compared-with-flixabi%C3%A2-and-remsima%C3%A2
#1
Changsoo Lee, Min Jeong, JongAh Joanne Lee, Saebom Seo, Sung Chun Cho, Wei Zhang, Orlando Jaquez
As biosimilars enter the market, comparisons of product quality are needed. Manufacturing differences may lead to differences in critical quality attributes, which affect efficacy. Therefore, critical quality attributes (structure and biological activity) of Remicade® and of 2 biosimilar products (Flixabi®/Renflexis® and Remsima®/Inflectra®) were determined. We assessed binding to tumor necrosis factor in a fluorescence competitive binding assay; potency in a luciferase reporter gene assay; percentages of galactosylated glycan, afucose plus high mannosylated glycans, and charged glycan; FcγRIIIa (CD16) binding (assessed by 3 methods); and antibody-dependent cell-mediated cytotoxicity (ADCC) in the NK92-CD16a cell line and in peripheral blood mononuclear cells (PBMC)...
June 22, 2017: MAbs
https://www.readbyqxmd.com/read/28630095/antibody-dependent-nk-cell-activation-differentially-targets-ebv-infected-cells-in-lytic-cycle-and-bystander-b-lymphocytes-bound-to-viral-antigen-containing-particles
#2
María López-Montañés, Elisenda Alari-Pahissa, Jordi Sintes, José E Martínez-Rodríguez, Aura Muntasell, Miguel López-Botet
NK cells have been reported to respond against EBV-infected B cells in the lytic cycle and to control the viral infection involving IFN-γ secretion. Early reports proposed a role for NK cell Ab-dependent cellular cytotoxicity (ADCC) triggered via FcγR-IIIA (CD16) in the response to EBV. In the current study, we revisited this issue, showing that serum from EBV(+) individuals triggered vigorous NK cell degranulation and cytokine production (i.e., TNF-α and IFN-γ) against EBV-infected cells, enhancing NK cell activation...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28629572/3t-diffusion-weighted-mri-in-the-response-assessment-of-colorectal-liver-metastases-after-chemotherapy-correlation-between-adc-value-and-histological-tumour-regression-grading
#3
Francescamaria Donati, Piero Boraschi, Federica Pacciardi, Rosa Cervelli, Maura Castagna, Lucio Urbani, Fabio Falaschi, Davide Caramella
PURPOSE: The purpose of the study was to correlate the apparent diffusion coefficient (ADC) values of diffusion-weighted MR imaging (DW-MRI) by 3T device with the histological tumour regression grading (TRG) analysis of colorectal liver metastases after preoperative chemotherapy. MATERIALS AND METHODS: Our study included thirty-five patients with colorectal liver metastases who had undergone MRI by 3T device (GE DISCOVERY MR750; GE Healthcare) after preoperative chemotherapy...
June 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28624584/antibody-dependent-nk-cell-degranulation-as-a-marker-for-assessing-antibody-dependent-cytotoxicity-against-pandemic-2009-influenza-a-h1n1-infection-in-human-plasma-and-influenza-vaccinated-transchromosomic-bovine-intravenous-immunoglobulin-therapy
#4
Brian J Morrison, Jessica A Roman, Thomas C Luke, Nishith Nagabhushana, Kanakatte Raviprakash, Maya Williams, Peifang Sun
This study describes an antibody-dependent NK cell degranulation assay, as a biomarker to assess antibody-dependent cellular cytotoxicity (ADCC) response in influenza plasma and for antibody therapies against influenza infection. The concentration of neutralizing antibodies (NAbs) against the hemagglutinin receptor of influenza viruses is a current determinant in protection against infection, particularly following receipt of the seasonal influenza vaccine. However, this is a limited assessment of protection, because: (i) NAb titers that incur full protection vary; and (ii) NAb titers do not account for the entire breadth of antibody responses against viral infection...
June 15, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28623459/blockade-of-cd112r-and-tigit-signaling-sensitizes-human-natural-killer-cell-functions
#5
Feng Xu, Alexander Sunderland, Yue Zhou, Richard D Schulick, Barish H Edil, Yuwen Zhu
Trastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. We found that all PVR-like receptors are expressed on human NK cells, and only TIGIT is preferentially expressed on the CD16+ NK cell subset. Disrupting the interactions of PVR-like receptors with their ligands on cancer cells regulates NK cell activity...
June 16, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28615419/dimeric-fc%C3%AE-receptor-enzyme-linked-immunosorbent-assay-to-study-hiv-specific-antibodies-a-new-look-into-breadth-of-fc%C3%AE-receptor-antibodies-induced-by-the-rv144-vaccine-trial
#6
Milla R McLean, Vijaya Madhavi, Bruce D Wines, P Mark Hogarth, Amy W Chung, Stephen J Kent
Ab-dependent cellular cytotoxicity (ADCC) responses are of growing interest in the HIV vaccine field but current cell-based assays are usually difficult to reproduce across laboratories. We developed an ELISA and multiplex assay to model the cross-linking of Fcγ receptors (FcγR) by Abs, which is required to initiate an ADCC response. Our FcγR dimer ELISA readily detected Abs in samples from two separate cohorts of the partially efficacious Thai RV144 HIV vaccine efficacy trial. The FcγR dimer-binding Abs induced by the RV144 regimen correlated well with a functional measure of ADCC as well as IgG subclasses...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28615199/impaired-downregulation-of-nkg2d-ligands-by-nef-protein-from-elite-controllers-sensitizes-hiv-1-infected-cells-to-adcc
#7
Nirmin Alsahafi, Jonathan Richard, Jérémie Prévost, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Daniel E Kaufmann, Mark Brockman, Andrés Finzi
HIV-1 Nef clones isolated from a rare subset of HIV-1-infected elite controllers (EC), with the ability to suppress viral load to undetectable levels in the absence of antiretroviral therapy, are unable to fully downregulate CD4 from the plasma membrane of CD4+ T cells. Residual CD4 left at the plasma membrane allows Env-CD4 interaction, which leads to increased exposure of Env CD4-induced epitopes and increases susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated largely by natural killer (NK) cells, which control their activation status through the cumulative signals received through activating and inhibitory receptors...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28605680/surrogate-cd16-expressing-effector-cell-lines-for-determining-the-bioactivity-of-therapeutic-monoclonal-antibodies
#8
Shalom A Gurjar, Jeremy P Derrick, Rebecca J Dearman, Robin Thorpe, Simon Hufton, Ian Kimber, Meenu Wadhwa
Traditional antibody dependent cellular cytotoxicity (ADCC) assays use donor derived natural killer (NK) or peripheral blood mononuclear cells, but donor genetic variability and the technically challenging nature of the assay means that alternative in vitro assay formats are required. We explored the utility of two reporter gene cell lines, the J2 and J9, as surrogate effector cells for ADCC assays. Both express the ADCC relevant Fcγ receptor CD16, crosslinking of which leads to firefly luciferase expression...
June 9, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28598823/preclinical-data-on-the-combination-of-cisplatin-and-anti-cd70-therapy-in-non-small-cell-lung-cancer-as-an-excellent-match-in-the-era-of-combination-therapy
#9
Julie Jacobs, Vanessa Deschoolmeester, Christian Rolfo, Karen Zwaenepoel, Jolien Van den Bossche, Christophe Deben, Karen Silence, Hans de Haard, Christophe Hermans, Sylvie Rottey, Christel Vangestel, Filip Lardon, Evelien Smits, Patrick Pauwels
In contrast to the negligible expression of the immunomodulating protein CD70 in normal tissue, we have demonstrated constitutive overexpression of CD70 on tumor cells in a subset of primary non-small cell lung cancer (NSCLC) biopsies. This can be exploited by CD70-targeting antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies. Early clinical trials of these antibodies have already shown promising results in CD70-positive malignancies.In this study, we explored the potential of cisplatin to induce CD70 expression in NSCLC...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28594149/myb-mybl1-mybl2-and-nfib-gene-alterations-and-myc-overexpression-in-salivary-gland-adenoid-cystic-carcinoma
#10
Kana Fujii, Takayuki Murase, Shintaro Beppu, Kosuke Saida, Hisashi Takino, Ayako Masaki, Kei Ijichi, Kimihide Kusafuka, Yoshiyuki Iida, Tetsuro Onitsuka, Yasushi Yatabe, Nobuhiro Hanai, Yasuhisa Hasegawa, Hiroshi Inagaki
AIMS: Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and the long-term prognosis is poor. In this study, we examined alterations of AdCC-associated genes, MYB, MYBL1, MYBL2, and NFIB, and their target molecules including MYC. The results were correlated to clinicopathological profile of the patients. METHODS AND RESULTS: Using paraffin tumor sections from 33 cases of salivary gland AdCC, we performed a detailed fluorescence in situ hybridization (FISH) analysis for gene splits and fusions of MYB, MYBL1, MYBL2, and NFIB...
June 8, 2017: Histopathology
https://www.readbyqxmd.com/read/28593989/pentavalent-hiv-1-vaccine-protects-against-simian-human-immunodeficiency-virus-challenge
#11
Todd Bradley, Justin Pollara, Sampa Santra, Nathan Vandergrift, Srivamshi Pittala, Chris Bailey-Kellogg, Xiaoying Shen, Robert Parks, Derrick Goodman, Amanda Eaton, Harikrishnan Balachandran, Linh V Mach, Kevin O Saunders, Joshua A Weiner, Richard Scearce, Laura L Sutherland, Sanjay Phogat, Jim Tartaglia, Steven G Reed, Shiu-Lok Hu, James F Theis, Abraham Pinter, David C Montefiori, Thomas B Kepler, Kristina K Peachman, Mangala Rao, Nelson L Michael, Todd J Suscovich, Galit Alter, Margaret E Ackerman, M Anthony Moody, Hua-Xin Liao, Georgia Tomaras, Guido Ferrari, Bette T Korber, Barton F Haynes
The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian-human immunodeficiency virus (SHIV) challenge...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28593386/prostate-specific-membrane-antigen-pet-imaging-and-immunohistochemistry-in-adenoid-cystic-carcinoma-%C3%AF-a-preliminary-analysis
#12
Thomas J W Klein Nulent, Robert J J van Es, Gerard C Krijger, Remco de Bree, Stefan M Willems, Bart de Keizer
BACKGROUND: Adenoid cystic carcinoma (AdCC) of the head and neck is an uncommon malignant epithelial tumour of the secretory glands. Many patients develop slowly growing local recurrence and/or distant metastasis, for which treatment options are limited. A retrospective analysis of 9 AdCC patients was conducted to analyse the visualization of AdCC on PSMA PET/CT and to investigate the expression of PSMA on primary, recurrent and metastatic AdCC tumour tissue using immunohistochemistry...
June 7, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28592534/comprehensive-cross-clade-characterization-of-antibody-mediated-recognition-complement-mediated-lysis-and-cell-mediated-cytotoxicity-of-hiv-1-envelope-specific-antibodies-towards-the-eradication-of-the-hiv-1-reservoir
#13
Shariq Mujib, Jun Liu, A K M Nur-Ur Rahman, Jordan A Schwartz, Phil Bonner, Feng Yun Yue, Mario A Ostrowski
Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. Here, we determined the ability of twelve well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1, belonging to clades A, B, C and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28576848/identification-of-fc-gamma-receptor-glycoforms-that-produce-differential-binding-kinetics-for-rituximab
#14
Jerrard M Hayes, Asa Frostell, Robert Karlsson, Steffen Müller, Silvia Millan-Martin, Martin Pauers, Franziska Reuss, Eoin Cosgrave, Cecilia Anneren, Gavin P Davey, Pauline M Rudd
Fc gamma receptors (FcyR) bind the Fc region of antibodies and therefore play a prominent role in antibody-dependent cell-based immune responses such as ADCC, CDC and ADCP. The immune effector cell activity is directly linked to a productive molecular engagement of FcyRs where both the protein and glycan moiety of antibody and receptor can affect the interaction and in the present study we focus on the role of the FcyR glycans in this interaction. We provide a complete description of the glycan composition of Chinese hamster ovary (CHO) expressed human Fcy receptors RI (CD64), RIIa Arg131/His131 (CD32a), RIIb (CD32b) and RIIIa Phe158/Val158 (CD16a) and analyze the role of the glycans in the binding mechanism with IgG...
June 2, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28574487/cd123-target-validation-and-preclinical-evaluation-of-adcc-activity-of-anti-cd123-antibody-csl362-in-combination-with-nks-from-aml-patients-in-remission
#15
L H Xie, M Biondo, S J Busfield, A Arruda, X Yang, G Vairo, M D Minden
Despite the heterogeneity of acute myeloid leukemia (AML), overexpression of the interleukin-3 receptor-α (CD123) on both the more differentiated leukemic blast and leukemic stem cells (LSCs) provides a therapeutic target for antibody treatment. Here we present data on the potential clinical activity of the monoclonal antibody CSL362, which binds to CD123 with high affinity. We first validated the expression of CD123 by 100% (52/52) of patient samples and the correlation of NPM1 and FLT3-ITD mutations with the high frequency of CD123 in AML...
June 2, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28574482/immunologic-and-virologic-mechanisms-for-partial-protection-from-intravenous-challenge-by-an-integration-defective-siv-vaccine
#16
Chu Wang, Chunlai Jiang, Nan Gao, Kaikai Zhang, Donglai Liu, Wei Wang, Zhe Cong, Chuan Qin, Vitaly V Ganusov, Guido Ferrari, Celia LaBranche, David C Montefiori, Wei Kong, Xianghui Yu, Feng Gao
The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity elicited by attenuated SIV vaccines, we developed an integration-defective SIV (idSIV) vaccine by inactivating integrase, mutating sequence motifs critical for integration, and inserting the cytomegalovirus (CMV) promoter for more efficient expression in the SIVmac239 genome...
June 2, 2017: Viruses
https://www.readbyqxmd.com/read/28561935/clinicopathologic-characteristics-of-kit-and-protein-kinase-c-%C3%AE-expression-in-adenoid-cystic-carcinoma-comparison-with-chromophobe-renal-cell-carcinoma-and-gastrointestinal-stromal-tumor
#17
Cheol Keun Park, Won Kyu Kim, Hoguen Kim
AIMS: KIT overexpression is frequently observed in adenoid cystic carcinomas (AdCCs), chromophobe renal cell carcinomas (ChRCCs), and gastrointestinal stromal tumor (GISTs). Persistent KIT activation has been reported to be mediated by protein kinase C (PKC)-δ in a subset of colon cancers with wild-type KIT overexpression and by PKC-θ in GISTs with mutant KIT overexpression. To elucidate the clinical implications of PKC-δ and PKC-θ expression in KIT-expressing tumors, we investigated the expression of KIT, PKC-δ, and PKC-θ in AdCCs and ChRCCs in comparison to GISTs...
May 31, 2017: Histopathology
https://www.readbyqxmd.com/read/28542406/human-igg3-with-extended-half-life-does-not-improve-fc-gamma-receptor-mediated-cancer-antibody-therapies-in-mice
#18
Rens Braster, Simran Grewal, Remco Visser, Helga K Einarsdottir, Marjolein van Egmond, Gestur Vidarsson, Marijn Bögels
BACKGROUND: Current anti-cancer therapeutic antibodies that are used in the clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These antibodies bind with high affinity to the target antigen and are efficient in activating the immune system via IgG Fc receptors and/or complement. In addition to IgG1, three more isotypes are present in humans, of which IgG3 has been found to be superior compared to human IgG1 in inducing antibody dependent cell cytotoxicity (ADCC), phagocytosis or activation of complement in some models...
2017: PloS One
https://www.readbyqxmd.com/read/28542350/t0001-a-variant-of-tnfr2-fc-fusion-protein-exhibits-improved-fc-effector-functions-through-increased-binding-to-membrane-bound-tnf%C3%AE
#19
Yijun Shen, Gang Li, Chunying Gu, Ben Chen, Aihua Chen, Hua Li, Bei Gao, Chencai Liang, Jingsong Wu, Tong Yang, Li Jin, Yong Su
T0001 is a recombinant human TNFR-Fc fusion protein mutant; it exhibits higher affinity to TNFα than etanercept and is now being tested in a Phase 1 study in China (ClinicalTrials.gov Identifier: NCT02481180). T0001 can inhibit the binding of soluble TNFα (sTNFα) or membrane-bound TNFα (mTNFα) to TNF receptors. When bound to mTNFα, the Fc-bearing TNFα antagonists have the potential to induce Fc-mediated effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as outside-to-inside signals (apoptosis mainly)...
2017: PloS One
https://www.readbyqxmd.com/read/28539449/anti-hiv-1-adcc-antibodies-following-latency-reversal-and-treatment-interruption
#20
Wen Shi Lee, Anne B Kristensen, Thomas A Rasmussen, Martin Tolstrup, Lars Østergaard, Ole S Søgaard, Bruce D Wines, P Mark Hogarth, Arnold Reynaldi, Miles P Davenport, Sean Emery, Janaki Amin, David A Cooper, Virginia L Kan, Julie Fox, Henning Gruell, Matthew S Parsons, Stephen J Kent
There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC...
May 24, 2017: Journal of Virology
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