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https://www.readbyqxmd.com/read/27923642/development-of-ifn-%C3%AE-secretory-elispot-based-assay-for-screening-of-adcc-responses
#1
Ashwini Shete, Poonam Suryawanshi, Chetan Chavan, Archana Kulkarni, Sheela Godbole, Manisha Ghate, Madhuri Thakar
Antibody Dependent Cell mediated Cytotoxicity has been established as one of the important protective immune mechanisms against HIV making it essential to evaluate it while testing immunogenicity of emerging vaccine candidates. IFN-γ secretory ELISPOT assay, widely used for evaluation of CTL response in HIV vaccine trials, was adapted for measuring ADCC responses and the results were compared with the standard ICS based assays. IFN-γ responses by both the methods were compared in plasma samples of 23 HIV infected individuals against Env and Gag peptides using granulocytes as antigen presenting cells...
December 3, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27914742/influenza-virus-specific-antibody-dependent-cellular-cytoxicity-induced-by-vaccination-or-natural-infection
#2
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
#3
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
#4
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/27896563/broad-spectrum-antiviral-properties-of-andrographolide
#5
REVIEW
Swati Gupta, K P Mishra, Lilly Ganju
Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC)...
November 28, 2016: Archives of Virology
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
#6
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/27856634/fc-engineering-approaches-to-enhance-the-agonism-and-effector-functions-of-an-anti-ox40-antibody
#7
Di Zhang, Monica V Goldberg, Mark L Chiu
Agonistic antibodies directed against immunostimulatory receptors belonging to the tumor necrosis factor receptor (TNFR) superfamily are emerging as promising cancer immunotherapies. Several Fc engineering approaches were discovered recently that can augment the anti-tumor activities of TNFR antibodies by enhancing their agonistic activities and/or effector functions. In this study, we evaluated and compared these approaches for their effects on an anti-OX40 antibody. Both S267E/L328F and V12 mutations of an anti-OX40 antibody can facilitate enhanced binding to FcγRIIB and result in increased FcγRIIB crosslinking mediated agonist activity...
November 17, 2016: Journal of Biological Chemistry
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
#8
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/27853288/enhancing-virion-tethering-by-bst2-sensitizes-productively-and-latently-hiv-infected-t-cells-to-adcc-mediated-by-broadly-neutralizing-antibodies
#9
Tram N Q Pham, Sabelo Lukhele, Frédéric Dallaire, Gabrielle Perron, Éric A Cohen
Binding of anti-HIV antibodies (Abs) to envelope (Env) glycoproteins on infected cells can mark them for elimination via antibody-dependent cell-mediated cytotoxicity (ADCC). BST2, a type I interferon (IFN)-stimulated restriction factor that anchors nascent Env-containing virions at the surface of infected cells has been shown to enhance ADCC functions. In a comprehensive analysis of ADCC potency by neutralizing anti-HIV Abs (NAbs), we show in this study that NAbs are capable of mediating ADCC against HIV-infected T cells with 3BNC117, PGT126 and PG9 being most efficient...
November 17, 2016: Scientific Reports
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
#10
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/27835615/modulation-of-innate-and-adaptive-cellular-immunity-relevant-to-hiv-1-vaccine-design-by-seminal-plasma
#11
Kevin J Selva, Stephen J Kent, Matthew S Parsons
OBJECTIVES: Mucosal exposure to HIV-1 infection generally occurs in the presence of semen. Immunomodulation by seminal plasma (SP) is well described in the reproductive biology literature. Little is known, however, about the impact of SP on innate and adaptive anti-HIV-1 cellular immunity. DESIGN: This study investigated the effects of SP on immune responses considered important for prophylactic HIV-1 vaccine development, namely innate and adaptive cellular immunity mediated by NK cells and T-cells, respectively...
November 9, 2016: AIDS
https://www.readbyqxmd.com/read/27828973/immunization-with-brugia-malayi-myosin-as-heterologous-dna-prime-protein-boost-induces-protective-immunity-against-b-malayi-infection-in-mastomys-coucha
#12
Jyoti Gupta, Sweta Misra, Shailja Misra-Bhattacharya
The current control strategies employing chemotherapy with diethylcarbamazine, ivermectin and albendazole have reduced transmission in some filaria-endemic areas, there is growing interest for complementary approaches, such as vaccines especially in light of threat of parasite developing resistance to mainstay drugs. We earlier demonstrated recombinant heavy chain myosin of B. malayi (Bm-Myo) as a potent vaccine candidate whose efficacy was enhanced by heterologous DNA prime/protein boost (Myo-pcD+Bm-Myo) vaccination in BALB/c mice...
2016: PloS One
https://www.readbyqxmd.com/read/27827447/molecular-basis-for-epitope-recognition-by-non-neutralizing-anti-gp41-antibody-f240
#13
Neelakshi Gohain, William D Tolbert, Chiara Orlandi, Jonathan Richard, Shilei Ding, Xishan Chen, Daniel A Bonsor, Eric J Sundberg, Wuyuan Lu, Krishanu Ray, Andrés Finzi, George K Lewis, Marzena Pazgier
Antibody-dependent cell-mediated cytotoxicity (ADCC) by non-neutralizing antibodies (nnAbs) specific to the HIV envelope (Env) glycoproteins present at the surface of virus sensitized or infected cells plays a role in the effective adaptive immune response to HIV. Here, we explore the molecular basis for the epitope at the disulfide loop region (DLR) of the principal immunodominant domain of gp41, recognized by the well-known nnAb F240. Our structural studies reveal details of the F240-gp41 interface and describe a structure of DLR that is distinct from known conformations of this region studied in the context of either CD4-unliganded Env trimer or the gp41 peptide in the unbound state...
November 9, 2016: Scientific Reports
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
#14
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
#15
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/27806135/a-trematode-parasite-derived-growth-factor-binds-and-exerts-influences-on-host-immune-functions-via-host-cytokine-receptor-complexes
#16
Azad A Sulaiman, Katarzyna Zolnierczyk, Ornampai Japa, Jonathan P Owen, Ben C Maddison, Richard D Emes, Jane E Hodgkinson, Kevin C Gough, Robin J Flynn
The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27793919/cell-surface-antibody-retention-influences-in-vivo-antitumor-activity-mediated-by-antibody-dependent-cellular-cytotoxicity
#17
Masahiro Ikeda, Kazunori Kato, Miki Yamaguchi, Hirofumi Hamada, Kazuyasu Nakamura, Yoshiyuki Sugimoto
BACKGROUND: Multiple factors affect the in vivo antitumor activity of antibody-based therapeutics; however, the influence of cell surface retention on antibody-dependent cellular cytotoxicity (ADCC) is not fully understood. Here we evaluated the importance of cell surface antibody retention in antitumor activity mediated by ADCC in vivo. MATERIALS AND METHODS: Two mAbs against tumor-associated calcium signal transducer 2 (TACSTD2/TROP2), AR47A6.4.2 and Pr1E11, were used...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27771962/humoral-antibody-responses-to-hiv-viral-proteins-and-to-cd4-among-hiv-controllers-rapid-and-typical-progressors-in-an-hiv-positive-patient-cohort
#18
Elizabeth Fink, Katherine Fuller, Brian Agan, Edward A Berger, Andrew Saphire, Gerald V Quinnan, John H Elder
The purpose of this study was to assess humoral antibody responses as a function of disease progression (DP) in a well-defined HIV(+) cohort. We quantified antibodies to HIV-1 gp120, Gag, and CD4 receptor by enzyme-linked immunosorbent assay in sera from a cohort of 97 HIV(+) subjects at defined stages of DP. We also measured antibody-dependent cellular cytotoxicity (ADCC) as a function of the clinical status of the patients. We purified antibodies to CD4 and gp120 and assessed them for specificity, ability to block gp120 binding to target cells, ability to block virus infection, and ability to facilitate ADCC...
December 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27757306/mechanisms-of-leukemia-resistance-to-antibody-dependent-cellular-cytotoxicity
#19
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
#20
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
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