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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/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
#3
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/29644082/characterisation-of-anifrolumab-a-fully-human-anti-interferon-receptor-antagonist-antibody-for-the-treatment-of-systemic-lupus-erythematosus
#4
Jeffrey M Riggs, Richard N Hanna, Bhargavi Rajan, Kamelia Zerrouki, Jodi L Karnell, Divya Sagar, Inna Vainshtein, Erika Farmer, Kimberly Rosenthal, Chris Morehouse, Melissa de Los Reyes, Kevin Schifferli, Meina Liang, Miguel A Sanjuan, Gary P Sims, Roland Kolbeck
Objective: We investigated the mechanistic and pharmacological properties of anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha receptor 1 (IFNAR1) monoclonal antibody in development for SLE. Methods: IFNAR1 surface expression and internalisation on human monocytes before and after exposure to anifrolumab were assessed using confocal microscopy and flow cytometry. The effects of anifrolumab on type I IFN pathway activation were assessed using signal transducer and activator of transcription 1 (STAT1) phosphorylation, IFN-stimulated response element-luciferase reporter cell assays and type I IFN gene signature induction...
2018: Lupus Science & Medicine
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
#5
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/29619555/prognostic-significance-of-1p36-locus-deletion-in-adenoid-cystic-carcinoma-of-the-salivary-glands
#6
Petr Šteiner, Simon Andreasen, Petr Grossmann, Lukáš Hauer, Tomáš Vaněček, Markéta Miesbauerová, Thalita Santana, Katalin Kiss, David Slouka, Alena Skálová
Adenoid cystic carcinoma (AdCC) of the salivary glands is characterized by MYB-NFIB or MYBL1-NFIB fusion, prolonged but relentlessly progressive clinical course with frequent recurrences, and development of distant metastasis resulting in high long-term mortality. Currently, no effective therapy is available for patients with advanced non-resectable and/or metastatic disease. Complicating the clinical management of this patient group is the lack of prognostic markers. The purpose of this study is to investigate the prognostic value of 1p36 loss in patients with AdCC...
April 4, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29609506/ublituximab-for-the-treatment-of-cd20-positive-b-cell-malignancies
#7
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
#8
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/29602284/common-antibody-dependent-cell-mediated-cytotoxicity-adcc-antibody-epitopes-of-hiv-1-crf01_ae-env-and-gag-in-early-hiv-1-infected-individuals
#9
Soraya Sangjan, Silawun Ampol, Guo Jia-Jun, Sutchana Tabprasit, Navin Horthongkham, Thippawan Chuenchitra, Pattama Ekpo, Wannee Kantakamalakul
BACKGROUND: There have been a few studies aimed at identifying epitopes of ADCC-inducing antibodies when compared to those of neutralizing antibodies and cytotoxic T lymphocytes against a variety of HIV-1 clades. OBJECTIVE: To map the common ADCC epitopes of HIV-1 CRF01_AE. METHODS: We screened 65 sera of confirmed early HIV-1 CRF01_AE infected individuals for ADCC antibody against gp120 utilizing an EGFP-CEM-NKr flow cytometric assay. Sera with high ADCC antibody were then examined against ADCC epitopes using the complete HIV-1 CRF01_AE gp160- and subtype A Gag-overlapping peptide sets which were divided into 7 pools:E1-E7 and 5 pools:G1-G5, respectively...
March 31, 2018: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/29600574/quantitative-assessment-of-mab-fc-glycosylation-of-cqa-importance-by-capillary-electrophoresis
#10
Marton Szigeti, Jeff Chapman, Beata Borza, Andras Guttman
The attached carbohydrates at the highly conserved asparagine-linked glycosylation site in the CH 2 domain of the fragment crystallizable (Fc) region of monoclonal antibody therapeutics can play an essential role in their mechanism of action, including ADCC, CDC, anti-inflammatory functions, and serum half-life. Thus, this particular glycosylation represents one of the important critical quality attributes (CQA) of therapeutic monoclonal antibodies, which should be closely monitored and controlled during all stages of biopharmaceutical manufacturing...
March 30, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29593050/ecd4-ig-variants-that-more-potently-neutralize-hiv-1
#11
Ina Fetzer, Matthew R Gardner, Meredith E Davis-Gardner, Neha R Prasad, Barnett Alfant, Jesse A Weber, Michael Farzan
The HIV-1 entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralizes all HIV-1, HIV-2 and SIV isolates that it has been tested against, suggesting that it may be useful in clinical settings where antibody escape is a concern. Here we characterize three new eCD4-Ig variants, each with different architectures and each utilizing D1...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29593039/il-15-stimulated-natural-killer-cells-clear-hiv-1-infected-cells-following-latency-reversal-ex-vivo
#12
Carolina Garrido, Maria Abad-Fernandez, Marina Tuyishime, Justin J Pollara, Guido Ferrari, Natalia Soriano-Sarabia, David M Margolis
Current efforts towards HIV eradication include approaches to augment immune recognition and elimination of persistently infected cells following latency reversal. Natural killer (NK) cells, the main effectors of the innate immune system, recognize and clear targets using different mechanisms than CD8+ T cells, offering an alternative or complementary approach for HIV clearance strategies. We assessed the impact of IL-15 treatment on NK cell function and the potential of stimulated NK cells to clear the HIV reservoir...
March 28, 2018: Journal of Virology
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
#13
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/29572470/transcriptomic-signatures-of-nk-cells-suggest-impaired-responsiveness-in-hiv-1-infection-and-increased-activity-post-vaccination
#14
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/29568351/targeting-of-embryonic-annexin-a2-expressed-on-ovarian-and-breast-cancer-by-the-novel-monoclonal-antibody-2448
#15
Simeon Cua, Heng Liang Tan, Wey Jia Fong, Angela Chin, Ally Lau, Vanessa Ding, Zhiwei Song, Yuansheng Yang, Andre Choo
Monoclonal antibodies (mAbs) play an increasingly important role in cancer therapy. To address the wide heterogeneity of the disease, the identification of novel antigen targets and the development of mAbs against them are needed. Our lab previously generated a panel of mAbs against human embryonic stem cells (hESC) using a whole cell immunization approach in mice. These mAbs can potentially target oncofetal antigens and be repurposed for antibody or antibody drug conjugate (ADC) therapy. From this panel, the novel IgG1 2448 was found to bind surface antigens on hESC and multiple cancer cell lines...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29559570/uninfected-bystander-cells-impact-the-measurement-of-hiv-specific-antibody-dependent-cellular-cytotoxicity-responses
#16
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/29554481/the-transgenic-chicken-derived-anti-cd20-monoclonal-antibodies-exhibits-greater-anti-cancer-therapeutic-potential-with-enhanced-fc-effector-functions
#17
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
https://www.readbyqxmd.com/read/29552307/characterization-of-7a7-an-anti-mouse-egfr-monoclonal-antibody-proposed-to-be-the-mouse-equivalent-of-cetuximab
#18
Xuzhi He, Jazmina L Cruz, Shannon Joseph, Nicola Pett, Hui Yi Chew, Zewen K Tuong, Satomi Okano, Gabrielle Kelly, Margaret Veitch, Fiona Simpson, James W Wells
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29548607/impact-of-pre-existing-immunity-on-the-induction-of-functional-cross-reactive-anti-hemagglutinin-stalk-antibodies-following-vaccination-with-an-as03-adjuvanted-pandemic-h1n1-vaccine
#19
Sarah M Tete, Åsne Jul-Larsen, Sina Rostami, Turid Helen Felli Lunde, Hanne Søland, Florian Krammer, Rebecca J Cox
The 2009 pandemic H1N1 (A(H1N1)pdm09) virus had a highly divergent hemagglutinin (HA) compared to pre-2009 seasonal H1N1 strains. Most peoples were immunologically naïve to the A(H1N1)pdm09, although hospital workers were exposed early in the pandemic before pandemic vaccines became available. Here, we evaluated how pre-existing antibodies influence the induction of cross-functional HA stalk antibodies following A(H1N1)pdm09 vaccination. Fifty-six healthcare workers vaccinated with AS03 adjuvanted A(H1N1)pdm09 vaccine were chosen by their pre-vaccination priming status (primed HI titers ≥ 40 or unprimed < 40)...
March 13, 2018: Vaccine
https://www.readbyqxmd.com/read/29541868/selection-of-a-ligand-binding-neutralizing-antibody-assay-for-benralizumab-comparison-with-an-antibody-dependent-cell-mediated-cytotoxicity-adcc-cell-based-assay
#20
Yuling Wu, Ahmad Akhgar, Jia J Li, Binbing Yu, Cecil Chen, Nancy Lee, Wendy I White, Lorin K Roskos
Assessment of anti-drug antibodies (ADAs) for neutralizing activity is important for the clinical development of biopharmaceuticals. Two types of neutralizing antibody (NAb) assays (competitive ligand-binding assay [CLBA] and cell-based assay [CBA]) are commonly used to characterize neutralizing activities. To support the clinical development of benralizumab, a humanized, anti-interleukin-5 receptor α, anti-eosinophil monoclonal antibody, we developed and validated a CLBA and a CBA. The CLBA and CBA were compared for sensitivity, drug tolerance, and precision to detect NAbs in serum samples from clinical trials...
March 14, 2018: AAPS Journal
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