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Antibody dependent cellular cytotoxicity

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https://www.readbyqxmd.com/read/28225449/ifn-%C3%AE-augments-natural-killer-mediated-antibody-dependent-cellular-cytotoxicity-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-major-histocompatibility-complex-class-1-downregulation
#1
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct natural killer (NK) cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon major histocompatibility complex class 1 (MHC-1) downregulation capacity. Here, we investigated if antibody-dependent cellular cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α prestimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1-infected patients (ART-suppressed or elite controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1-infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
March 13, 2017: AIDS
https://www.readbyqxmd.com/read/28192188/hepatitis-c-virus-induced-nk-cell-activation-causes-metzincin-mediated-cd16-cleavage-and-impaired-antibody-dependent-cytotoxicity
#2
Barbara Oliviero, Stefania Mantovani, Stefania Varchetta, Dalila Mele, Giulia Grossi, Serena Ludovisi, Elisa Nuti, Armando Rossello, Mario U Mondelli
BACKGROUND & AIMS: The Fc receptor family for IgG type III (FcγRIII, CD16) is an activating receptor on natural killer (NK) cells and an essential mediator of antibody-dependent cellular cytotoxicity (ADCC). There is only limited information on its role during chronic hepatitis C virus (HCV) infection. We studied CD16 expression in relation to NK cell functional activity in HCV-infected patients and sought mechanistic insights into virus-induced modulation. METHODS: NK cell CD16 expression and activation status were evaluated ex vivo by flow cytometry in HCV-infected patients and healthy controls (HC) as well as in vitro after co-culture with HCV-infected Huh 7...
February 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28184223/fc-engineering-for-developing-therapeutic-bispecific-antibodies-and-novel-scaffolds
#3
REVIEW
Hongyan Liu, Abhishek Saxena, Sachdev S Sidhu, Donghui Wu
Therapeutic monoclonal antibodies have become molecules of choice to treat autoimmune disorders, inflammatory diseases, and cancer. Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells (T cell, natural killer cell, or macrophage cell) toward target cells have shown great potential to maximize the benefits of antibody therapy. In the past decade, many novel concepts to generate bispecific and multispecific antibodies have evolved successfully into a range of formats from full bispecific immunoglobulin gammas to antibody fragments...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28179536/hiv-aids-vaccine-candidates-based-on-replication-competent-recombinant-poxvirus-nyvac-c-kc-expressing-trimeric-gp140-and-gag-derived-vlps-or-lacking-the-viral-molecule-b19-that-inhibits-type-i-interferon-activate-relevant-hiv-1-specific-b-and-t-cell-immune
#4
Juan García-Arriaza, Beatriz Perdiguero, Jonathan L Heeney, Michael S Seaman, David C Montefiori, Nicole L Yates, Georgia D Tomaras, Guido Ferrari, Kathryn E Foulds, Mario Roederer, Steven G Self, Bhavesh Borate, Raphael Gottardo, Sanjay Phogat, Jim Tartaglia, Susan W Barnett, Brian Burke, Anthony D Cristillo, Deborah E Weiss, Carter Lee, Karen V Kibler, Bertram L Jacobs, Ralf Wagner, Song Ding, Giuseppe Pantaleo, Mariano Esteban
The non-replicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120), Gag-Pol-Nef antigens (NYVAC-C) showed in phase I clinical trials limited immunogenicity. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4(+) and CD8(+) T cells, here we compared the HIV-1-specific immunogenicity elicited in non-human primates immunized with two replicating NYVAC vectors that have been modified by the insertion of K1L and C7L vaccinia viral host-range genes and express clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC)...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28157429/chimeric-anti-human-podoplanin-antibody-nz-12-of-lambda-light-chain-exerts-higher-antibody-dependent-cellular-cytotoxicity-and-complement-dependent-cytotoxicity-compared-with-nz-8-of-kappa-light-chain
#5
Mika K Kaneko, Shinji Abe, Satoshi Ogasawara, Yuki Fujii, Shinji Yamada, Takeshi Murata, Hiroaki Uchida, Hideaki Tahara, Yasuhiko Nishioka, Yukinari Kato
Podoplanin (PDPN), a type I transmembrane 36-kDa glycoprotein, is expressed not only in normal cells, such as renal epithelial cells (podocytes), lymphatic endothelial cells, and pulmonary type I alveolar cells, but also in cancer cells, including brain tumors and lung squamous cell carcinomas. Podoplanin activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets, and the podoplanin/CLEC-2 interaction facilitates blood/lymphatic vessel separation. We previously produced neutralizing anti-human podoplanin monoclonal antibody (mAb), clone NZ-1 (rat IgG2a, lambda), which neutralizes the podoplanin/CLEC-2 interaction and inhibits platelet aggregation and cancer metastasis...
February 3, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28138156/antibody-dependent-cell-cytotoxicity-adcc-immunotherapy-strategies-enhancing-effector-nk-cells
#6
REVIEW
Maria Carmen Ochoa, Luna Minute, Inmaculada Rodriguez, Saray Garasa, Elisabeth Perez-Ruiz, Susana Inogés, Ignacio Melero, Pedro Berraondo
Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only NK cells but also other CD16(+) subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells. An approach to enhance antitumor activity is to act on effector cells so they are increased in their numbers or enhanced in their individual (on a cell per cell basis) ADCC performance...
January 31, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28133794/hiv-antibodies-for-treatment-of-hiv-infection
#7
REVIEW
David M Margolis, Richard A Koup, Guido Ferrari
The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28122982/lack-of-adcc-breadth-of-human-non-neutralizing-anti-hiv-1-antibodies
#8
Timothée Bruel, Florence Guivel-Benhassine, Valérie Lorin, Hugues Lortat-Jacob, Françoise Baleux, Katia Bourdic, Nicolas Noël, Olivier Lambotte, Hugo Mouquet, Olivier Schwartz
: Anti-HIV-1 non-neutralizing antibodies (nnAbs) capable of antibody-dependent cellular cytotoxicity (ADCC) have been identified as a protective immune correlate in the RV144 vaccine efficacy trial. Broadly neutralizing antibodies (bNAbs) also mediate ADCC in cell culture and rely on their Fc region for optimal efficacy in animal models. Here, we selected 9 monoclonal nnAbs and 5 potent bNAbs, targeting various epitopes and conformations of the gp120/41 complex, and analyzed the potency of the two types of antibodies to bind and eliminate HIV-1-infected cells in culture...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28118850/humans-from-wuchereria-bancrofti-endemic-area-elicit-substantial-immune-response-to-proteins-of-the-filarial-parasite-brugia-malayi-and-its-endosymbiont-wolbachia
#9
Ruchi Jha, Mamta Gangwar, Dhanvantri Chahar, Anand Setty Balakrishnan, Mahendra Pal Singh Negi, Shailja Misra-Bhattacharya
BACKGROUND: In the past, immune responses to several Brugia malayi immunodominant antigens have been characterized in filaria-infected populations; however, little is known regarding Wolbachia proteins. We earlier cloned and characterized few B. malayi (trehalose-6-phosphate phosphatase, Bm-TPP and heavy chain myosin, BmAF-Myo) and Wolbachia (translation initiation factor-1, Wol Tl IF-1 and NAD(+)-dependent DNA ligase, wBm-LigA) proteins and investigated the immune responses, which they triggered in animal models...
January 24, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28102191/a-broadly-protective-therapeutic-antibody-against-influenza-b-virus-with-two-mechanisms-of-action
#10
Ning Chai, Lee R Swem, Summer Park, Gerald Nakamura, Nancy Chiang, Alberto Estevez, Rina Fong, Lynn Kamen, Elviza Kho, Mike Reichelt, Zhonghua Lin, Henry Chiu, Elizabeth Skippington, Zora Modrusan, Jeremy Stinson, Min Xu, Patrick Lupardus, Claudio Ciferri, Man-Wah Tan
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28100618/influence-of-the-envelope-gp120-phe-43-cavity-on-hiv-1-sensitivity-to-adcc-responses
#11
Jérémie Prévost, Daria Zoubchenok, Jonathan Richard, Maxime Veillette, Beatriz Pacheco, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Kiat Ruxrungtham, Torsak Bunupuradah, Sodsai Tovanabutra, Kwan-Ki Hwang, M Anthony Moody, Barton F Haynes, Mattia Bonsignori, Joseph Sodroski, Daniel E Kaufmann, George M Shaw, Agnès L Chenine, Andrés Finzi
: HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to CD4-bound state...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#12
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28088123/antibody-dependent-cellular-cytotoxicity-and-influenza-virus
#13
REVIEW
Hillary A Vanderven, Sinthujan Jegaskanda, Adam K Wheatley, Stephen J Kent
Antibodies are a key defence against influenza infection and disease, but neutralizing antibodies are often strain-specific and of limited utility against divergent or pandemic viruses. There is now considerable evidence that influenza-specific antibodies with Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can assist in the clearance of influenza infection in vitro and in animal models. Further, ADCC-mediating antibodies that recognize a broad array of influenza strains are common in humans, likely as a result of being regularly exposed to influenza infections...
January 11, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28087106/charge-variant-analysis-of-proposed-biosimilar-to-trastuzumab
#14
Pravinkumar Dakshinamurthy, Pavithra Mukunda, Bhargav Prasad Kodaganti, Bharath Ravindra Shenoy, Bairavabalakumar Natarajan, Amol Maliwalave, Vivek Halan, Sathyabalan Murugesan, Sunit Maity
Trastuzumab is a humanized monoclonal antibody (mAb) employed for the treatment of HER2 Positive Breast Cancer. A HER2 overexpressing tumor cell binds to Trastuzumab and attracts immune cells which lead to induction of Antibody Dependent Cellular Cytotoxicity (ADCC) by binding to Fc receptors (CD16a or FcγRIIIa) on an effector cell, such as natural killer (NK) cells. The most commonly expressed receptor on NK cell is CD16a which binds to the Fc portion of Trastuzumab. The ligand-independent HER2-HER3 dimerization is the most potent stimulator of downstream pathways for regulation of cell growth and survival...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28074864/a-novel-monoclonal-antibody-targeting-coxsackie-virus-and-adenovirus-receptor-inhibits-tumor-growth-in-vivo
#15
Manabu Kawada, Hiroyuki Inoue, Masunori Kajikawa, Masahito Sugiura, Shuichi Sakamoto, Sakiko Urano, Chigusa Karasawa, Ihomi Usami, Mitsuru Futakuchi, Tohru Masuda
To create a new anti-tumor antibody, we conducted signal sequence trap by retrovirus-meditated expression method and identified coxsackie virus and adenovirus receptor (CXADR) as an appropriate target. We developed monoclonal antibodies against human CXADR and found that one antibody (6G10A) significantly inhibited the growth of subcutaneous as well as orthotopic xenografts of human prostate cancer cells in vivo. Furthermore, 6G10A also inhibited other cancer xenografts expressing CXADR, such as pancreatic and colorectal cancer cells...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28060015/ifn-%C3%AE-augments-nk-mediated-antibody-dependent-cellular-cytotoxicity-adcc-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-mhc-i-downregulation
#16
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct NK cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon MHC-I downregulation capacity. Here, we investigated if Antibody Dependent Cellular Cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α pre-stimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1 infected subjects (ART-suppressed or Elite Controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1 infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28031227/cetuximab-resistance-in-head-and-neck-cancer-is-mediated-by-egfr-k521-polymorphism
#17
Friederike Braig, Malte Kriegs, Beate Habel, Minna Voigtlaender, Tobias Grob, Karina Biskup, Véronique Blanchard, Markus Sack, Anja Thalhammer, Isabel Ben Batalla, Ingke Braren, Simon Laban, Antje Danielczyk, Steffen Goletz, Elzbieta Jakubowicz, Bruno Märkl, Martin Trepel, Rainald Knecht, Kristoffer Riecken, Boris Fehse, Sonja Loges, Carsten Bokemeyer, Mascha Binder
Head and neck squamous cell carcinomas (HNSCC) exhibiting resistance to the EGFR targeting drug cetuximab poses a challenge to their effective clinical management. Here we report a specific mechanism of resistance in this setting based upon the presence of a single nucleotide polymorphism encoding EGFR-K521 (K-allele), which is expressed in >40% of HNSCC cases. Patients expressing the K-allele showed significantly shorter progression-free survival upon palliative treatment with cetuximab plus chemotherapy or radiation...
December 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/28029136/application-of-lectin-array-technology-for-biobetter-characterization-its-correlation-with-fc%C3%AE-riii-binding-and-adcc
#18
Markus Roucka, Klaus Zimmermann, Markus Fido, Andreas Nechansky
Lectin microarray technology was applied to compare the glycosylation pattern of the monoclonal antibody MB311 expressed in SP2.0 cells to an antibody-dependent cellular cytotoxic effector function (ADCC)-optimized variant (MB314). MB314 was generated by a plant expression system that uses genetically modified moss protoplasts (Physcomitrella patens) to generate a de-fucosylated version of MB311. In contrast to MB311, no or very low interactions of MB314 with lectins Aspergillus oryzae l-fucose (AOL), Pisum sativum agglutinin (PSA), Lens culinaris agglutinin (LCA), and Aleuria aurantia lectin (AAL) were observed...
December 24, 2016: Microarrays
https://www.readbyqxmd.com/read/28027665/three-year-durability-of-immune-responses-induced-by-hiv-dna-and-hiv-modified-vaccinia-virus-ankara-and-effect-of-a-late-hiv-mva-boost-in-tanzanian-volunteers
#19
Agricola Joachim, Patricia J Munseri, Charlotta Nilsson, Muhammad Bakari, Said Aboud, Eligius F Lyamuya, Teghesti Tecleab, Valentina Liakina, Gabriella Scarlatti, Merlin Robb, Patricia Earl, Bernard Moss, Britta Wahren, Fred Mhalu, Guido Ferarri, Eric Sandström, Gunnel Biberfeld
We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization three years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100)...
December 27, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28018347/advances-in-therapeutic-fc-engineering-modulation-of-igg-associated-effector-functions-and-serum-half-life
#20
REVIEW
Abhishek Saxena, Donghui Wu
Today, monoclonal immunoglobulin gamma (IgG) antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs) is achieved through both its antigen-binding fragment (Fab) and crystallizable fragment (Fc). Fab can specifically recognize tumor-associated antigen (TAA) and thus modulate TAA-linked downstream signaling pathways that may lead to the inhibition of tumor growth, induction of tumor apoptosis, and differentiation...
2016: Frontiers in Immunology
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