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https://www.readbyqxmd.com/read/27914742/influenza-virus-specific-antibody-dependent-cellular-cytoxicity-induced-by-vaccination-or-natural-infection
#1
Rory D de Vries, Nella J Nieuwkoop, Mark Pronk, Erwin de Bruin, Geert Leroux-Roels, Elisabeth G W Huijskens, Rob S van Binnendijk, Florian Krammer, Marion P G Koopmans, Guus F Rimmelzwaan
Influenza viruses are responsible for substantial morbidity and mortality during seasonal epidemics. Vaccination is the most effective method to prevent infection, however due to antigenic drift of the viral surface protein hemagglutinin (HA), annual influenza virus vaccination is required. In addition to seasonal viruses, certain (avian) influenza A viruses of other subtypes, like H5N1 or H7N9, cause sporadic zoonotic infections. Therefore, the availability of game-changing novel vaccines that induce "universal" immune responses to a wide variety of influenza A virus subtypes is highly desirable...
November 30, 2016: Vaccine
https://www.readbyqxmd.com/read/27913647/diversity-of-antiviral-igg-effector-activities-observed-in-hiv-infected-and-vaccinated-subjects
#2
Yunda Huang, Guido Ferrari, Galit Alter, Donald N Forthal, John C Kappes, George K Lewis, J Christopher Love, Bhavesh Borate, Linda Harris, Kelli Greene, Hongmei Gao, Tran B Phan, Gary Landucci, Brittany A Goods, Karen G Dowell, Hao D Cheng, Chris Bailey-Kellogg, David C Montefiori, Margaret E Ackerman
Diverse Ab effector functions mediated by the Fc domain have been commonly associated with reduced risk of infection in a growing number of nonhuman primate and human clinical studies. This study evaluated the anti-HIV Ab effector activities in polyclonal serum samples from HIV-infected donors, VAX004 vaccine recipients, and healthy HIV-negative subjects using a variety of primary and cell line-based assays, including Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cell-mediated viral inhibition, and Ab-dependent cellular phagocytosis...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#3
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27861156/an-nk-cell-line-hank-expressing-high-levels-of-granzyme-and-engineered-to-express-the-high-affinity-cd16-allele
#4
Caroline Jochems, James W Hodge, Massimo Fantini, Rika Fujii, Y Maurice Morillon Ii, John W Greiner, Michelle R Padget, Sarah R Tritsch, Kwong Yok Tsang, Kerry S Campbell, Hans Klingemann, Laurent Boissel, Shahrooz Rabizadeh, Patrick Soon-Shiong, Jeffrey Schlom
Natural killer (NK) cells are known to play a role in mediating innate immunity, in enhancing adaptive immune responses, and have been implicated in mediating anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) by reactivity of CD16 with the Fc region of human IgG1 antibodies. The NK-92 cell line, derived from a lymphoma patient, has previously been well characterized and adoptive transfer of irradiated NK-92 cells has demonstrated safety and shown preliminary evidence of clinical benefit in cancer patients...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27856192/nk-cell-degranulation-as-a-marker-for-measuring-antibody-dependent-cytotoxicity-in-neutralizing-and-non-neutralizing-human-sera-from-dengue-patients
#5
Peifang Sun, Brian J Morrison, Charmagne G Beckett, Zhaodong Liang, Nishith Nagabhushana, An Li, Kevin R Porter, Maya Williams
The study assessed antibody-dependent NK cell degranulation, a biomarker relevant to antibody-dependent cell cytotoxicity (ADCC), to analyze dengue immune sera. We first determined binding intensity of patient sera to the surface of DENV-infected cells and examined the types of antigens expressed on infected cells. Antigens from pre-membrane (PreM) and envelope (E), but not from NS proteins were detected on the surface of infected cells. After adding NK cells to infected target cells previously treated with patient sera, rapid NK cell degranulation was observed...
November 14, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27846736/small-molecule-cd4-mimetics-sensitize-hiv-1-infected-cells-to-adcc-by-antibodies-elicited-by-multiple-envelope-glycoprotein-immunogens-in-non-human-primates
#6
Shilei Ding, Myriam M Verly, Amy Princiotto, Bruno Melillo, Tony Moody, Todd Bradley, David Easterhoff, Michele Roger, Beatrice H Hahn, Navid Madani, Amos B Smith Iii, Barton F Haynes, Joseph G Sodroski, Andres Finzi
Recent studies have linked antibody Fc-mediated effector functions with control of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) infections. Interestingly, the presence of antibodies with potent antibody-dependent cellular cytotoxicity (ADCC) activity in RV144 vaccine trial participants correlated inversely with HIV-1 acquisition risk. These antibodies were recently found to recognize epitopes on the HIV-1 envelope (Env) glycoprotein exposed upon Env-CD4 binding. Accordingly, small molecule CD4-mimetics (CD4mc) that induce Env to sample the CD4-bound conformation were shown to sensitize HIV-1-infected cells to ADCC mediated by sera from HIV-1-infected individuals...
November 16, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27825135/cd19-specific-triplebody-spm-1-engages-nk-and-%C3%AE-%C3%AE-t-cells-for-rapid-and-efficient-lysis-of-malignant-b-lymphoid-cells
#7
Christian B Schiller, Todd A Braciak, Nadja C Fenn, Ursula J E Seidel, Claudia C Roskopf, Sarah Wildenhain, Annemarie Honegger, Ingo A Schubert, Alexandra Schele, Kerstin Lämmermann, Georg H Fey, Uwe Jacob, Peter Lang, Karl-Peter Hopfner, Fuat S Oduncu
Triplebodies are antibody-derived recombinant proteins carrying 3 antigen-binding domains in a single polypeptide chain. Triplebody SPM-1 was designed for lysis of CD19-bearing malignant B-lymphoid cells through the engagement of CD16-expressing cytolytic effectors, including NK and γδ T cells.SPM-1 is an optimized version of triplebody ds(19-16-19) and includes humanization, disulfide stabilization and the removal of potentially immunogenic sequences. A three-step chromatographic procedure yielded 1.7 - 5...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27814766/antibody-dependent-cd56-t-cell-responses-are-functionally-impaired-in-long-term-hiv-1-infection
#8
Xueying Fan, Liyan Zhu, Hua Liang, Zhe Xie, Xiangbo Huang, Shuo Wang, Tao Shen
BACKGROUND: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in slowing human immunodeficiency virus type-1 (HIV-1) disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression...
November 4, 2016: Retrovirology
https://www.readbyqxmd.com/read/27757306/mechanisms-of-leukemia-resistance-to-antibody-dependent-cellular-cytotoxicity
#9
Leonid Dubrovsky, Elliott Joseph Brea, Dmitry Pankov, Emily Casey, Tao Dao, Cheng Liu, David A Scheinberg
Specific immunotherapy for acute leukemia remains a great unmet need. Native unmodified monoclonal antibody therapies, while promising, are inadequately effective for these malignancies, and multiple mechanisms for failure have been described. Antibody-dependent cellular cytotoxicity or phagocytosis is the primary modality of mAb-mediated cell killing in vivo, but ultimately leads to relapse of the leukemias, in model systems and in humans. By use of a T-cell receptor mimic mAb ESKM, derived against a WT1 peptide expressed in complex with HLA-A*02:01, whose only mechanism of therapeutic action is ADCC, we evaluated the mechanisms of leukemic relapse from its potent therapeutic action in mouse xenograft models of human leukemia...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27756784/tgf%C3%AE-r1-blockade-with-galunisertib-ly2157299-enhances-anti-neuroblastoma-activity-of-anti-gd2-antibody-dinutuximab-ch14-18-with-natural-killer-cells
#10
Hung C Tran, Zesheng Wan, Michael A Sheard, Jianping Sun, Jeremy R Jackson, Jemily Malvar, Yibing Xu, Larry Wang, Richard Sposto, Eugene S Kim, Shahab Asgharzadeh, Robert C Seeger
PURPOSE: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma. EXPERIMENTAL DESIGN: TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis...
October 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27746785/ha-antibody-mediated-fc%C3%AE-riiia-activity-is-both-dependent-on-fcr-engagement-and-interactions-between-ha-and-sialic-acids
#11
Freek Cox, Ted Kwaks, Boerries Brandenburg, Martin H Koldijk, Vincent Klaren, Bastiaan Smal, Hans J W M Korse, Eric Geelen, Lisanne Tettero, David Zuijdgeest, Esther J M Stoop, Eirikur Saeland, Ronald Vogels, Robert H E Friesen, Wouter Koudstaal, Jaap Goudsmit
Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to the in vivo protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27739418/prognostic-and-therapeutic-values-of-tumor-necrosis-factor-alpha-in-hepatocellular-carcinoma
#12
Hongmei Wang, Jianmin Liu, Xuemei Hu, Shanshan Liu, Baojun He
BACKGROUND Hepatocellular carcinoma (HCC) causes many deaths worldwide every year, especially in Asia. It is characterized by high malignancy, recurrence, and short survival time. Inflammation is closely related to the initiation and development of HCC. Tumor necrosis factor-α (TNF-α), an essential inflammatory mediator, has been studied as a potential therapy target in many cancers. However, its potential role in HCC diagnosis and therapy is still unclear. MATERIAL AND METHODS In our study, we detected the TNF-α expression in both human HCC tumor tissue and HCC cell lines HepG2 and HuH7...
October 14, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27712994/identification-of-high-affinity-anti-cd16a-allotype-independent-human-antibody-domains
#13
Wei Li, Hongjia Yang, Dimiter S Dimitrov
CD16A (FcγRIIIA) is an activating receptor mostly expressed on natural killer (NK) cells and monocytes/macrophages. It can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) through low-affinity interaction with human immunoglobulin G (IgG) Fc. It can also mediate cell lysis if NK cells are guided by bispecific killer cells engagers (BiKEs). BiKEs showed some success in clinical trials of cancer and are promising candidate therapeutics. However, currently reported BiKEs are based on antibody fragments (scFvs) of relatively large size...
October 3, 2016: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/27699264/depletion-of-major-pathogenic-cells-in-asthma-by-targeting-crth2
#14
Tao Huang, Meredith Hazen, Yonglei Shang, Meijuan Zhou, Xiumin Wu, Donghong Yan, Zhonghua Lin, Margaret Solon, Elizabeth Luis, Hai Ngu, Yongchang Shi, Arna Katewa, David F Choy, Nandhini Ramamoorthi, Erick R Castellanos, Mercedesz Balazs, Min Xu, Wyne P Lee, Marissa L Matsumoto, Jian Payandeh, Joseph R Arron, Jo-Anne Hongo, Jianyong Wang, Isidro Hötzel, Cary D Austin, Karin Reif
Eosinophilic inflammation and Th2 cytokine production are central to the pathogenesis of asthma. Agents that target either eosinophils or single Th2 cytokines have shown benefits in subsets of biomarker-positive patients. More broadly effective treatment or disease-modifying effects may be achieved by eliminating more than one inflammatory stimulator. Here we present a strategy to concomitantly deplete Th2 T cells, eosinophils, basophils, and type-2 innate lymphoid cells (ILC2s) by generating monoclonal antibodies with enhanced effector function (19A2) that target CRTh2 present on all 4 cell types...
May 19, 2016: JCI Insight
https://www.readbyqxmd.com/read/27698437/intravital-imaging-reveals-improved-kupffer-cell-mediated-phagocytosis-as-a-mode-of-action-of-glycoengineered-anti-cd20-antibodies
#15
Capucine L Grandjean, Fabricio Montalvao, Susanna Celli, David Michonneau, Beatrice Breart, Zacarias Garcia, Mario Perro, Olivier Freytag, Christian A Gerdes, Philippe Bousso
Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27670158/cd16-is-indispensable-for-antibody-dependent-cellular-cytotoxicity-by-human-monocytes
#16
Wei Hseun Yeap, Kok Loon Wong, Noriko Shimasaki, Esmeralda Chi Yuan Teo, Jeffrey Kim Siang Quek, Hao Xiang Yong, Colin Phipps Diong, Antonio Bertoletti, Yeh Ching Linn, Siew Cheng Wong
Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27659529/induction-of-anti-egfr-immune-response-with-mimotopes-identified-from-a-phage-display-peptide-library-by-panitumumab
#17
Aidong Wang, Ming Cui, Hong Qu, Jiabo Di, Zaozao Wang, Jiadi Xing, Fan Wu, Wei Wu, Xicheng Wang, Lin Shen, Beihai Jiang, Xiangqian Su
The epidermal growth factor receptor (EGFR) is overexpressed in several epithelial tumors. Anti-EGFR humanized monoclonal antibodies, cetuximab and panitumumab, in combination with chemotherapy have improved the prognosis for patients with wild-type RAS tumors. To identify mimotopes of EGFR and develop mimotope-based EGFR vaccines, we screened a phage display peptide library with panitumumab. Two EGFR mimotopes P19 and P26, which could be recognized by panitumumab specifically, were isolated. To enhance the immune responses, we generated recombinant proteins of P19 or P26 fused to a heat-shock cognate protein 70 (Hsc70), and evaluated the efficacy of Hsc70-P19 and Hsc70-P26 as vaccines in vivo...
September 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27648129/pak2-promotes-migration-and-proliferation-of-salivary-gland-adenoid-cystic-carcinoma
#18
Wei-Wei Deng, Lei Wu, Lin-Lin Bu, Jian-Feng Liu, Yi-Cun Li, Si-Rui Ma, Guang-Tao Yu, Liang Mao, Wen-Feng Zhang, Zhi-Jun Sun
P21 activated kinase 2 (PAK2) is a member of Group I PAKs family and highly expressed in various cancers. Current studies have demonstrated that PAK2 played a pivotal role in tumor progression. However, the role of PAK2 in salivary adenoid cystic carcinoma is still unclear. This study aims to explore the expression and the function of PAK2 in AdCC. Human salivary gland tissue microarray, including 18 normal salivary glands (NSG), 12 pleomorphic adenoma (PMA) and 72 AdCC, and immunohistochemistry were used to evaluate the expression of PAK2...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27637890/the-human-cd38-monoclonal-antibody-daratumumab-shows-anti-tumor-activity-and-hampers-leukemia-microenvironment-interactions-in-chronic-lymphocytic-leukemia
#19
Alba Matas-Céspedes, Anna Vidal-Crespo, Vanina Rodriguez, Neus Villamor, Julio Delgado, Eva Giné, Heleia Roca-Ho, Pablo Menéndez, Elias Campo, Armando López-Guillermo, Dolors Colomer, Gaël Roué, Adrian Wiestner, Paul Whi Parren, Parul Doshi, Jeroen J Lammerts-van Bueren, Patricia Perez-Galan
PURPOSE: To establish a proof-of-concept for the efficacy of the anti-CD38 antibody daratumumab in the poor prognosis CD38+ CLL subtype. EXPERIMENTAL DESIGN: The mechanism of action of daratumumab was assessed in CLL primary cells and cell lines using peripheral blood mononuclear cells to analyze antibody-dependent cell cytotoxicity (ADCC), murine and human macrophages to study antibody-dependent cell phagocytosis (ADCP) or human serum to analyze complement-dependent cytotoxicity (CDC)...
September 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27633463/co-receptor-binding-site-antibodies-enable-cd4-mimetics-to-expose-conserved-anti-cluster-a-adcc-epitopes-on-hiv-1-envelope-glycoproteins
#20
Jonathan Richard, Beatriz Pacheco, Neelakshi Gohain, Maxime Veillette, Shilei Ding, Nirmin Alsahafi, William D Tolbert, Jérémie Prévost, Jean-Philippe Chapleau, Mathieu Coutu, Manxue Jia, Nathalie Brassard, Jongwoo Park, Joel R Courter, Bruno Melillo, Loïc Martin, Cécile Tremblay, Beatrice H Hahn, Daniel E Kaufmann, Xueling Wu, Amos B Smith, Joseph Sodroski, Marzena Pazgier, Andrés Finzi
Human immunodeficiency virus type 1 (HIV-1) has evolved a sophisticated strategy to conceal conserved epitopes of its envelope glycoproteins (Env) recognized by antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These antibodies, which are present in the sera of most HIV-1-infected individuals, preferentially recognize Env in its CD4-bound conformation. Accordingly, recent studies showed that small CD4-mimetics (CD4mc) able to "push" Env into this conformation sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera...
September 9, 2016: EBioMedicine
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