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https://www.readbyqxmd.com/read/28337279/agr2-promotes-the-proliferation-migration-and-regulates-epithelial-mesenchymal-transition-in-salivary-adenoid-cystic-carcinoma
#1
Si-Rui Ma, Liang Mao, Wei-Wei Deng, Yi-Cun Li, Lin-Lin Bu, Guang-Tao Yu, Wen-Feng Zhang, Zhi-Jun Sun
Salivary adenoid cystic carcinoma (AdCC) is a common head and neck cancer with the propensity for local spread and distant metastasis. In our previous study, elevated expression of Anterior gradient 2 (AGR2) was detected in head and neck squamous cell carcinoma (HNSCC), associated with epithelial-mesenchymal transition (EMT) and cancer stemness. However, to date, the expression and function of AGR2 in AdCC has yet to be elucidated. In the present study, human AdCC tissue microarrays including 18 cases of normal salivary gland (NSG), 12 cases of pleomorphic adenoma (PMA) and 72 cases of AdCC were employed for immunohistochemical staining analysis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28332900/fc-or-not-fc-that-is-the-question-antibody-fc-receptor-interactions-are-key-to-universal-influenza-vaccine-design
#2
Sinthujan Jegaskanda, Hillary A Vanderven, Adam K Wheatley, Stephen J Kent
A universal vaccine that provides long-lasting protection from both epidemic and pandemic influenza viruses remains the "holy grail" of influenza vaccine research. Though virus neutralization assays are the current benchmark of measuring vaccine effectiveness, it is clear that Fc-receptor functions can drastically improve the effectiveness of antibodies and vaccines in vivo. Antibodies that kill virus-infected cells and/or elicit an antiviral environment, termed antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, provide a link between the innate and adaptive immune response...
March 23, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#3
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28318221/crystal-structure-of-a-homogeneous-igg-fc-glycoform-with-the-n-glycan-designed-to-maximize-the-antibody-dependent-cellular-cytotoxicity
#4
Chia-Lin Chen, Jen-Chi Hsu, Chin-Wei Lin, Chia-Hung Wang, Ming-Hung Tsai, Chung-Yi Wu, Chi-Huey Wong, Che Ma
N-glycosylation on IgG modulates Fc conformation and effector functions. An IgG-Fc contains a human sialo-complex type (hSCT) glycan of biantennary structure with two α2,6-sialylations and without core-fucosylation is an optimized glycoform developed to enhance the antibody dependent cellular cytotoxicity (ADCC). hSCT modification not only enhances the binding affinity to Fc receptors in the presence of antigen, but also in some cases provides gain-of-function effector activity. We used enzymatic glyco-engineering to prepare an IgG-Fc with homogeneous hSCT attached to each CH2 domain, and solved its crystal structure...
March 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28314374/hiv-1-consensus-envelope-induced-broadly-binding-antibodies
#5
R Ryan Meyerhoff, Richard M Scearce, Damon F Ogburn, Brad Lockwood, Joy Pickeral, Masa Kuraoka, Kara Anasti, Joshua Eudailey, Amanda Eaton, Melissa Cooper, Kevin Wiehe, David C Montefiori, Georgia D Tomaras, Guido Ferrari, S Munir Alam, Hua-Xin Liao, Bette Korber, Feng Gao, Barton F Haynes
Antibodies that cross-react with multiple HIV-1 envelopes (Envs) are useful reagents for characterizing Env proteins and for soluble Env capture and purification assays. We previously reported ten murine monoclonal antibodies induced by group M consensus Env, CON-6 immunization. Each demonstrated broad cross-reactivity to recombinant Envs. Here we characterized the Env epitopes to which they bind. Seven mapped to linear epitopes in gp120, five at the Env N-terminus and two at the Env C-terminus. One antibody, 13D7, bound at the gp120 N-terminus (aa 30-42), reacted with HIV-1-infected CD4+ T cells, and when expressed in a human IgG1 backbone, mediated ADCC...
March 17, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28289219/modulating-igg-effector-function-by-fc-glycan-engineering
#6
Tiezheng Li, David J DiLillo, Stylianos Bournazos, John P Giddens, Jeffrey V Ravetch, Lai-Xi Wang
IgG antibodies contain a conserved N-glycosylation site on the Fc domain to which a complex, biantennary glycan is attached. The fine structures of this glycan modulate antibody effector functions by affecting the binding affinity of the Fc to diverse Fc receptor family members. For example, core fucosylation significantly decreases antibody-dependent cellular cytotoxicity (ADCC), whereas terminal α2,6-sialylation plays a critical role in the anti-inflammatory activity of human i.v. immunoglobulin therapy...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28275508/targeting-cd47-the-achievements-and-concerns-of-current-studies-on-cancer-immunotherapy
#7
COMMENT
Yuting Huang, Yuchi Ma, Peng Gao, Zhi Yao
Targeting CD47 is in the spotlight of cancer immunotherapy. Blocking CD47 triggers the recognition and elimination of cancer cells by the innate immunity. There are three CD47 antagonists in phase I clinical trials, but their potential efficacies are highly controversial. We raise our concern that NOD-based xenograft hosts tend to overestimate, while syngeneic mouse models could substantially underestimate the efficacy of anti-CD47 therapy. Such discrepancy may be resulted from specific reagent that alters CD47 clustering, and the highly variable avidities of interspecies and intraspecies CD47-SIRPα interaction...
February 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28274143/avelumab-combining-immune-checkpoint-inhibition-and-antibody-dependent-cytotoxicity
#8
Gerhard Hamilton, Barbara Rath
Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination...
April 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28239472/analyses-of-the-peripheral-immunome-following-multiple-administrations-of-avelumab-a-human-igg1-anti-pd-l1-monoclonal-antibody
#9
Renee N Donahue, Lauren M Lepone, Italia Grenga, Caroline Jochems, Massimo Fantini, Ravi A Madan, Christopher R Heery, James L Gulley, Jeffrey Schlom
BACKGROUND: Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#10
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28188909/extensive-preclinical-evaluation-of-an-infliximab-biosimilar-candidate
#11
M A Velasco-Velázquez, N Salinas-Jazmín, E Hisaki-Itaya, L Cobos-Puc, W Xolalpa, G González, A Tenorio-Calvo, N Piña-Lara, L C Juárez-Bayardo, L F Flores-Ortiz, E Medina-Rivero, N O Pérez, S M Pérez-Tapia
Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product...
February 7, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28182141/obinutuzumab-in-chronic-lymphocytic-leukemia-design-development-and-place-in-therapy
#12
REVIEW
Othman Al-Sawaf, Kirsten Fischer, Anja Engelke, Natali Pflug, Michael Hallek, Valentin Goede
For decades, treatment of chronic lymphocytic leukemia (CLL) has been based on chemotherapy. This changed when the first CD20 antibody rituximab was introduced. Since 2008, the combination of chemotherapy and CD20 antibodies has become the standard of care for most patients, and a significant fraction of patients had very long-lasting remissions after chemoimmunotherapy. Despite the improvement of response rates and overall survival (OS) by the use of chemoimmunotherapy, most CLL patients will relapse eventually...
2017: Drug Design, Development and Therapy
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
#13
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 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28154890/single-nucleotide-polymorphisms-in-the-fc%C3%AE-r3a-and-tap1-genes-impact-adcc-in-cynomolgus-monkey-pbmcs
#14
Jonathan C Sanford, Hong Wu, Yasmina Abdiche, Julie A Harney, Javier Chaparro-Riggers, Karissa Adkins
Phenotypic variability is often observed in cynomolgus monkeys on preclinical studies and may, in part, be driven by genetic variability. However, the role of monkey genetic variation remains largely unexplored in the context of drug response. This study evaluated genetic variation in cynomolgus monkey FcγR3A and TAP1 genes and the potential impact of identified polymorphisms on antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. Studies in humans have demonstrated that a single nucleotide polymorphism (SNP), F158V, in FcγR3A can influence response to rituximab through altered ADCC and that SNPs in TAP1/2 decrease natural killer (NK) cell activity against major histocompatibility complex (MHC) class I deficient cells, potentially through altered ADCC...
February 3, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28154569/regulation-of-nk-cell-activation-and-effector-functions-by-the-il-12-family-of-cytokines-the-case-of-il-27
#15
REVIEW
Norberto Walter Zwirner, Andrea Ziblat
Natural killer (NK) cells are characterized by their ability to detect and induce apoptosis of susceptible target cells and by secretion of immunoregulatory cytokines such as IFN-γ. Activation of these effector functions is triggered upon recognition of tumor and pathogen (mostly virus)-infected cells and because of a bidirectional cross talk that NK cells establish with other cells of myeloid origin such as dendritic cells (DC) and macrophages. A common characteristic of these myeloid cells is their ability to secrete different members of the IL-12 family of cytokines such as IL-12, IL-23, and IL-27 and cytokines such as IL-15 and IL-18...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28154562/indian-long-term-non-progressors-show-broad-adcc-responses-with-preferential-recognition-of-v3-region-of-envelope-and-a-region-from-tat-protein
#16
Archana Kulkarni, Swarali Kurle, Ashwini Shete, Manisha Ghate, Sheela Godbole, Vijaya Madhavi, Stephen J Kent, Ramesh Paranjape, Madhuri Thakar
HIV-specific antibody-dependent cell cytotoxicity (ADCC) is likely to be important in governing protection from human immunodeficiency virus (HIV) and slowing disease progression. Little is known about the ADCC responses to HIV-1 subtype C. We characterized ADCC responses in HIV-1 subtype C-infected Indian subjects with slow disease progression and identified the dominant antigenic regions recognized by these antibodies. ADCC responses were measured in plasma from 34 long-term non-progressors (LTNPs), who were asymptomatic and maintained CD4 count above 500 cells/mm(3) for the last 7 years in the absence of antiretroviral therapy (ART), and 58 ART naïve progressors with CD4 count <500 cells/mm(3) against overlapping HIV-1 peptides using a flow cytometry-based antibody-dependent natural killer (NK) cell activation assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28149769/a-novel-splice-site-mutation-of-cryba3-a1-gene-associated-with-congenital-cataract-in-a-chinese-family
#17
Meng-Han Wu, Yin-Hui Yu, Qin-Long Hao, Xiao-Hua Gong, Ke Yao
AIM: To identify the disease-causing mutation responsible for the presence of congenital cataract in a Chinese family. METHODS: The study recruited a four-generation Chinese pedigree affected by autosomal dominant congenital cataract (ADCC). Family history and the history of cataract extraction were recorded. Blood samples were collected from individuals for DNA extraction. Direct sequencing of congenital cataract-associated genes was performed. Single-strand conformational polymorphism and bioinformatic analysis were conducted to further study the mutation...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28138156/antibody-dependent-cell-cytotoxicity-immunotherapy-strategies-enhancing-effector-nk-cells
#18
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 natural killer (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...
February 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28122982/lack-of-adcc-breadth-of-human-non-neutralizing-anti-hiv-1-antibodies
#19
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/28119295/first-in-human-phase-1-study-of-margetuximab-mgah22-an-fc-modified-chimeric-monoclonal-antibody-in-patients-with-her2-positive-advanced-solid-tumors
#20
Y J Bang, G Giaccone, S A Im, D Y Oh, T M Bauer, J L Nordstrom, H Li, G R Chichili, P A Moore, S Hong, S J Stewart, J E Baughman, R J Lechleider, H A Burris
BACKGROUND: Margetuximab is an anti-HER2 antibody that binds with elevated affinity to both the lower and higher affinity forms of CD16A, an Fc-receptor important for antibody dependent cell-mediated cytotoxicity (ADCC) against tumor cells. A Phase 1 study was initiated to evaluate the toxicity profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of margetuximab in patients with HER2-overexpressing carcinomas. PATIENTS AND METHODS: Patients with HER2-positive breast or gastric cancer, or other carcinomas that overexpress HER2, for whom no standard therapy was available, were treated with margetuximab by intravenous infusion at doses of 0...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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