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Antibody dependent cellular cytotoxicity

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https://www.readbyqxmd.com/read/29666301/fratricide-of-nk-cells-in-daratumumab-therapy-for-multiple-myeloma-overcome-by-ex-vivo-expanded-autologous-nk-cells
#1
Yufeng Wang, Yibo Zhang, Tiffany Hughes, Jianying Zhang, Michael A Caligiuri, Don M Benson, Jianhua Yu
PURPOSE: Daratumumab and its use in combination with other agents is becoming a new standard of care for treatment of multiple myeloma (MM). We mechanistically studied how daratumumab acts on NK cells. EXPERIMENTAL DESIGN: Quantities of NK cells in peripheral blood (PB) and/or bone marrow (BM) of MM patients or healthy donors were examined by flow cytometry. NK cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29652548/ca125-suppresses-amatuximab-immune-effector-function-and-elevated-serum-levels-are-associated-with-reduced-clinical-response-in-first-line-mesothelioma-patients
#2
Nicholas C Nicolaides, Charles Schweizer, Elizabeth B Somers, Wenquan Wang, Shawn Fernando, Erin N Ross, Luigi Grasso, Raffit Hassan, J Bradford Kline
The tumor-shed antigen CA125 has recently been found to bind certain monoclonal antibodies (mAbs) and suppress immune-effector mediated killing through perturbation of the Fc domain with CD16a and CD32a Fc-γ activating receptors on immune-effector cells. Amatuximab is a mAb targeting mesothelin whose mechanism of action utilizes in part antibody-dependent cellular cytotoxicity (ADCC). It is being tested for its therapeutic activity in patients with mesothelioma in combination with first line standard-of-care...
April 13, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29651964/poly-l-arginine-enhancing-cytotoxicity-and-cellular-uptake-of-doxorubicin-and-necrotic-cell-death
#3
Bahareh Movafegh, Razieh Jalal, Zobeideh Mohammadi
OBJECTIVE: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. METHODS: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay...
April 11, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29651286/iga-targeting-human-immunodeficiency-virus-1-envelope-gp41-triggers-antibody-dependent-cellular-cytotoxicity-cross-clade-and-cooperates-with-gp41-specific-igg-to-increase-cell-lysis
#4
Maxence Duchemin, Marwa Khamassi, Lin Xu, Daniela Tudor, Morgane Bomsel
The protective efficacy of human immunodeficiency virus-1 (HIV-1) antibodies (Abs) remains mostly correlated with their in vitro neutralizing activity engaging their Fab region. However, anti-HIV-1 Abs also mediate a broad array of Fc-mediated effector functions including Ab-dependent cellular cytotoxicity (ADCC), which depend primarily on the Ab isotype. While ADCC is commonly associated with HIV-1 gp120 envelope-specific IgGs, whether IgAs, especially those targeting the HIV-1 gp41 envelope, also mediate ADCC remains elusive...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29643191/cd83-antibody-inhibits-human-b-cell-responses-to-antigen-as-well-as-dendritic-cell-mediated-cd4-t-cell-responses
#5
Kuan Y Wong, Rebecca Baron, Therese A Seldon, Martina L Jones, Alison M Rice, David J Munster
Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83+ human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29620716/viral-control-in-chronic-hiv-1-subtype-c-infection-is-associated-with-enrichment-of-p24-igg1-with-fc-effector-activity
#6
Amy Chung, Jenniffer M Makuba, Bongiwe Ndlovu, Anna Licht, Hannah Robinson, Yathisha Ramlakhan, Musie Ghebremichael, Tarylee Reddy, Philip Goulder, Bruce Walker, Thumbi Ndung'u, Galit Alter
OBJECTIVE: Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown. DESIGN: Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naïve participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential...
April 3, 2018: AIDS
https://www.readbyqxmd.com/read/29620542/donor-specific-hla-dq-antibodies-may-contribute-to-poor-graft-outcome-after-heart-transplantation
#7
Osama Omrani, Moheeb Alawwami, Jehad Buraiki, Nedim Selimovic
BACKGROUND: HLA-DQ donor-specific antibodies (DSA) are implicated in allograft dysfunction after renal and lung transplantation. Limited data exists on the impact of HLA-DQ antibodies on heart transplant patients. OBJECTIVE: To investigate the impact of DSA formation on allograft function and outcomes in heart transplant patients. DESIGN: Retrospective cohort study. SETTING: Collating post-transplantation patient data from computerized database in a tertiary hospital in Riyadh, Saudi Arabia from January 2006 to October 2014...
March 2018: Annals of Saudi Medicine
https://www.readbyqxmd.com/read/29609506/ublituximab-for-the-treatment-of-cd20-positive-b-cell-malignancies
#8
Hani M Babiker, Ashley E Glode, Laurence S Cooke, Daruka Mahadevan
Non-Hodgkin lymphoma (NHL) is the most common adult hematologic malignancy. Conventional methods of treatment are chemotherapy and radiation, which were associated with toxicities and lack of specificity. Potential cell surface targets for treatment of B-cell NHL (B-NHL) include CD19, CD20, and CD22 which are highly expressed on malignant B-cells. The development of monoclonal antibody (mAb) therapy directed against CD20 had the most clinical impact in the treatment of B-NHL. Early clinical trials with rituximab (RTX), the first chimeric mAb against CD20, showed efficacy and minimal toxicities...
April 3, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29605231/neutrophils-mediate-hiv-specific-antibody-dependent-phagocytosis-and-adcc
#9
Matthew J Worley, Kuangyu Fei, Adam J Lopez-Denman, Anthony D Kelleher, Stephen J Kent, Amy W Chung
There is growing evidence to support the role of Fc-mediated effector functions, such as Antibody-Dependent Cellular cytotoxicity (ADCC) and Antibody-Dependent Phagocytosis (ADP) in the protection and control of HIV. The RV144 trial and other recent HIV vaccine studies have highlighted the importance of ADCC responses in protection against HIV. The role of neutrophils, the most abundant leukocyte in the blood, has not been thoroughly evaluated for Fc-mediated effector functions to HIV. We optimized HIV-specific neutrophil ADCC and Antibody-Dependent Neutrophil Phagocytosis (ADNP) assays using freshly isolated primary human neutrophils from blood...
March 29, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29599908/regulatory-b-cells-induced-by-pancreatic-cancer-cell-derived-interleukin-18-promote-immune-tolerance-via-the-pd-1-pd-l1-pathway
#10
Yan Zhao, Ming Shen, Yecheng Feng, Ruizhi He, Xiaodong Xu, Yu Xie, Xiuhui Shi, Min Zhou, Shutao Pan, Min Wang, Xingjun Guo, Renyi Qin
Dysregulation of regulatory B cells (Bregs), a type of immunosuppressive lymphocyte, are associated with development of autoimmune diseases and cancers. Bregs produce immune tolerance-inducing cell surface molecules and tolerogenic cytokines (interleukin [IL]-10 and transforming growth factor-beta). We previously showed that levels of the inflammatory cytokine IL-18 were increased in patients with pancreatic cancer. In the present study study, we found that pancreatic cancer cell-derived IL-18 increases Breg-induced immunosuppression...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29593047/il-27r-signalling-mediates-early-viral-containment-and-impacts-innate-and-adaptive-immunity-after-chronic-lymphocytic-choriomeningitis-virus-infection
#11
James A Harker, Kurt A Wong, Simone Dallari, Phuc Bao, Aleksandr Dolgoter, Yeara Jo, Ellen J Wehrens, Monica Macal, Elina I Zuniga
Chronic viral infections represent a major challenge to host's immune response and a unique network of immunological elements, including cytokines, are required for their containment. By using a model persistent infection with the natural murine pathogen lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) we investigated the role of one such cytokine, interleukin 27 (IL-27), in the control of chronic infection. We found that IL-27R signalling promoted control of LCMV Cl13 as early as day 1 and 5 after infection and that il27p28 transcripts were rapidly elevated in multiple subsets of dendritic cells (DCs) and myeloid cells...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29584656/magnetic-graphene-oxide-for-dual-targeted-delivery-of-doxorubicin-and-photothermal-therapy
#12
Yu-Jen Lu, Pin-Yi Lin, Pei-Han Huang, Chang-Yi Kuo, K T Shalumon, Mao-Yu Chen, Jyh-Ping Chen
To develop a pH-sensitive dual targeting magnetic nanocarrier for chemo-phototherapy in cancer treatment, we prepared magnetic graphene oxide (MGO) by depositing Fe₃O₄ magnetic nanoparticles on graphene oxide (GO) through chemical co-precipitation. MGO was modified with polyethylene glycol (PEG) and cetuximab (CET, an epidermal growth factor receptor (EGFR) monoclonal antibody) to obtain MGO-PEG-CET. Since EGFR was highly expressed on the tumor cell surface, MGO-PEG-CET was used for dual targeted delivery an anticancer drug doxorubicin (DOX)...
March 27, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29581255/anti-ctla-4-therapy-requires-an-fc-domain-for-efficacy
#13
Jessica R Ingram, Olga S Blomberg, Mohammad Rashidian, Lestat Ali, Scott Garforth, Elena Fedorov, Alexander A Fedorov, Jeffrey B Bonanno, Camille Le Gall, Stephanie Crowley, Camilo Espinosa, Tamara Biary, Edmund J Keliher, Ralph Weissleder, Steven C Almo, Stephanie K Dougan, Hidde L Ploegh, Michael Dougan
Ipilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved "checkpoint"-blocking anticancer therapy. In mouse tumor models, the response to antibodies against CTLA-4 depends entirely on expression of the Fcγ receptor (FcγR), which may facilitate antibody-dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade remains unknown. To understand the role of CTLA-4 blockade in the complete absence of Fc-dependent functions, we developed H11, a high-affinity alpaca heavy chain-only antibody fragment (VHH) against CTLA-4...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29577600/quantification-of-number-of-cd38-sites-on-bone-marrow-plasma-cells-in-patients-with-light-chain-amyloidosis-and-smoldering-multiple-myeloma
#14
Katharina Kriegsmann, Tobias Dittrich, Brigitte Neuber, Mohamed H S Awwad, Ute Hegenbart, Hartmut Goldschmidt, Jens Hillengass, Dirk Hose, Anja Seckinger, Carsten Müller-Tidow, Anthony D Ho, Stefan Schönland, Michael Hundemer
BACKGROUND: Recent approaches in multiple myeloma (MM) treatment have targeted CD38. As antigen expression levels on plasma cells (PCs) were demonstrated to affect response to monoclonal antibody (mAb) treatment, a precise characterization of PC phenotype is warranted. METHODS: Anti-CD38 mAb (isatuximab) was tested for antibody-dependent cellular cytotoxicity (ADCC) in MM cell lines. Quantification of the number of sites (NOS) of CD38 on bone marrow PCs and other immune cells obtained from light chain (AL) amyloidosis (n=46) and smoldering multiple myeloma (SMM) patients (n=19) was performed with two different quantitative flow cytometry (QFCM) applications...
March 25, 2018: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29573261/development-of-novel-monoclonal-antibodies-to-dog-leukocyte-antigen-dr-displaying-direct-and-immune-mediated-cytotoxicity-toward-canine-lymphoma-cell-lines
#15
Marta Lisowska, Aleksandra Pawlak, Justyna Kutkowska, Wojciech Hildebrand, Maciej Ugorski, Andrzej Rapak, Arkadiusz Miazek
Spontaneous canine lymphoma (CL) has become a promising, nonrodent model for advancing the therapeutic strategies of human hematological malignancies. As new resources for veterinary and comparative studies on CL-associated antigens, we developed 2 novel mouse monoclonal antibodies, denoted B5 and E11, that recognized the canine major histocompatibility Class II DR antigens (dog leukocyte antigen DR). Using flow cytometry and solid phase immunoenzymatic assays, we showed that the antigens recognized by B5 and E11 were strongly expressed in several CL cell lines and the ex vivo canine neoplastic cells of B and mixed B/T immunophenotypes...
March 24, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29572470/transcriptomic-signatures-of-nk-cells-suggest-impaired-responsiveness-in-hiv-1-infection-and-increased-activity-post-vaccination
#16
Margaret C Costanzo, Dohoon Kim, Matthew Creegan, Kerri G Lal, Julie A Ake, Jeffrey R Currier, Hendrik Streeck, Merlin L Robb, Nelson L Michael, Diane L Bolton, Nicholas J Steers, Michael A Eller
Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK cells responding to models of direct cell recognition, ADCC, and cytokine activation have unique transcriptional fingerprints. Compared with healthy volunteers, individuals with chronic HIV-1 infection have higher expression of genes commonly associated with activation, and lower expression of genes associated with direct cell recognition and cytokine stimulation in their NK cells...
March 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29559570/uninfected-bystander-cells-impact-the-measurement-of-hiv-specific-antibody-dependent-cellular-cytotoxicity-responses
#17
Jonathan Richard, Jérémie Prévost, Amy E Baxter, Benjamin von Bredow, Shilei Ding, Halima Medjahed, Gloria G Delgado, Nathalie Brassard, Christina M Stürzel, Frank Kirchhoff, Beatrice H Hahn, Matthew S Parsons, Daniel E Kaufmann, David T Evans, Andrés Finzi
The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs)...
March 20, 2018: MBio
https://www.readbyqxmd.com/read/29556297/abnormal-populations-and-functions-of-natural-killer-cells-in-patients-with-myelodysplastic-syndromes
#18
Wei Zhang, Xinyan Xie, Huijing Mi, Jinwan Sun, Shaoxue Ding, Lijuan Li, Hui Liu, Huaquan Wang, Rong Fu, Zonghong Shao
Myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis that lead to leukemia. Disorders of the immune system serve important functions in the pathophysiology and progression of this disease. Different levels or mechanisms of natural killer (NK) cells in patients with MDS have been measured in previous studies, making it challenging to understand the pathogenesis of NK cytotoxicity. The present study investigated the frequency of NK cell-mediated antibody-dependent cellular cytotoxicity and explored the function of NK cells by their activating receptors, inhibition signals, degranulation and cytotoxicity factors...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29556226/host-immune-response-to-influenza-a-virus-infection
#19
REVIEW
Xiaoyong Chen, Shasha Liu, Mohsan Ullah Goraya, Mohamed Maarouf, Shile Huang, Ji-Long Chen
Influenza A viruses (IAVs) are contagious pathogens responsible for severe respiratory infection in humans and animals worldwide. Upon detection of IAV infection, host immune system aims to defend against and clear the viral infection. Innate immune system is comprised of physical barriers (mucus and collectins), various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, which provide first line of defense against IAV infection. The adaptive immunity is mediated by B cells and T cells, characterized with antigen-specific memory cells, capturing and neutralizing the pathogen...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29554481/the-transgenic-chicken-derived-anti-cd20-monoclonal-antibodies-exhibits-greater-anti-cancer-therapeutic-potential-with-enhanced-fc-effector-functions
#20
Young Min Kim, Jin Se Park, Sang Kyung Kim, Kyung Min Jung, Young Sun Hwang, Mookyoung Han, Hong Jo Lee, Hee Won Seo, Jeong-Yong Suh, Beom Ku Han, Jae Yong Han
Modern genetic techniques, enable the use of animal bioreactor systems for the production and functional enhancement of anti-cancer antibodies. Chicken is the most efficient animal bioreactor for the production of anti-cancer antibodies because of its relatively short generation time, plentiful reproductive capacity, and daily deposition in the egg white. Although several studies have focused on the production of anti-cancer antibodies in egg white, in-depth studies of the biological activity and physiological characteristics of transgenic chicken-derived anti-cancer antibodies have not been fully carried out...
March 13, 2018: Biomaterials
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