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Antibody dependent cellular cytotoxicity

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https://www.readbyqxmd.com/read/27903969/targeting-tissue-factor-as-a-novel-therapeutic-oncotarget-for-eradication-of-cancer-stem-cells-isolated-from-tumor-cell-lines-tumor-xenografts-and-patients-of-breast-lung-and-ovarian-cancer
#1
Zhiwei Hu, Jie Xu, Jijun Cheng, Elizabeth McMichael, Lianbo Yu, William E Carson Iii
Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899210/comparative-analysis-of-the-internalization-of-the-macrophage-receptor-sialoadhesin-in-human-and-mouse-primary-macrophages-and-cell-lines
#2
Marjorie De Schryver, Annelies Leemans, Isabel Pintelon, Davie Cappoen, Louis Maes, Guy Caljon, Paul Cos, Peter L Delputte
Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind with sialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal antibodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The latter characteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the fact that Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entry portal for phenotype-modulating or cytotoxic drugs...
November 21, 2016: Immunobiology
https://www.readbyqxmd.com/read/27891129/immunological-and-translational-aspects-of-nk-cell-based-antitumor-immunotherapies
#3
REVIEW
Maxim Shevtsov, Gabriele Multhoff
Natural killer (NK) cells play a pivotal role in the first line of defense against cancer. NK cells that are deficient in CD3 and a clonal T cell receptor (TCR) can be subdivided into two major subtypes, CD56(dim)CD16(+) cytotoxic and CD56(bright)CD16(-) immunoregulatory NK cells. Cytotoxic NK cells not only directly kill tumor cells without previous stimulation by cytotoxic effector molecules, such as perforin and granzymes or via death receptor interactions, but also act as regulatory cells for the immune system by secreting cytokines and chemokines...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-anti-tumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#4
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 mAb such as rituximab have proven highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody dependent cellular cytotoxicity, antibody dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-chronic lymphocytic leukemia (B-CLL). We hypothesized that immune stimulation through TLR7 agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term anti-tumor immune responses...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27872451/update-on-the-mechanisms-of-action-of-anti%C3%A2-tnf-%C3%AE-antibodies-and-their-clinical-implications-in-inflammatory-bowel-disease
#5
Piotr Eder, Krzysztof Linke, Janusz Witowski
The mechanisms of action of antitumor necrosis factor α (anti-TNF-α) antibodies in the therapy of inflammatory bowel disease (IBD) are not completely understood. Binding of antibodies to transmembrane TNF-α seems to be crucial for the induction of several cellular responses, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and reverse signaling. However, these processes alone do not fully explain the diversity of responses to anti-TNF-α therapy seen in different patients...
September 9, 2016: Polskie Archiwum Medycyny Wewnętrznej
https://www.readbyqxmd.com/read/27856634/fc-engineering-approaches-to-enhance-the-agonism-and-effector-functions-of-an-anti-ox40-antibody
#6
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/27853650/therapeutic-cd94-nkg2a-blockade-improves-natural-killer-cell-dysfunction-in-chronic-lymphocytic-leukemia
#7
Emily M McWilliams, Jennifer M Mele, Carolyn Cheney, Elizabeth A Timmerman, Faraz Fiazuddin, Ethan J Strattan, Xiaokui Mo, John C Byrd, Natarajan Muthusamy, Farrukh T Awan
Natural killer (NK)-cell count is predictive of chronic lymphoid leukemia (CLL) disease progression and their dysfunction is well documented, but the etiology of this is currently lacking. CLL cells have been shown to over-express HLA-E, the natural ligand for NKG2A expressed on NK-cells that generates a distinct negative signal relative to direct NK-cell cytotoxicity in other disease models. Utilizing a novel anti-NKG2A monoclonal blocking antibody (mAb), monalizumab, we explored the in vitro preclinical activity of targeting the NKG2A receptor, and the NKG2A/HLA-E interaction as a mechanism of tumor evasion in CLL patients...
2016: Oncoimmunology
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
#8
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
#9
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/27825564/genetic-markers-of-immunoglobulin-g-and-immunity-to-cytomegalovirus-in-patients-with-breast-cancer
#10
Janardan P Pandey, Aryan M Namboodiri, Sarumathi Mohan, Paul J Nietert, Lindsay Peterson
Human cytomegalovirus (CMV), a ubiquitous herpesvirus, has been implicated in the etiology of breast cancer. It is clear that not all people exposed to CMV are equally likely to develop this malignancy, implying the presence of host genetic factors that might modulate the cancer-spurring properties of the virus. CMV has evolved sophisticated strategies for evading host immunosurveillance. One strategy involves encoding decoy Fcγ receptors (FcγR) that thwart the Fcγ-mediated effector functions, such as antibody-dependent cellular cytotoxicity...
November 2, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27821119/insufficient-natural-killer-cell-responses-against-retroviruses-how-to-improve-nk-cell-killing-of-retrovirus-infected-cells
#11
REVIEW
Elisabeth Littwitz-Salomon, Ulf Dittmer, Kathrin Sutter
Natural killer (NK) cells belong to the innate immune system and protect against cancers and a variety of viruses including retroviruses by killing transformed or infected cells. They express activating and inhibitory receptors on their cell surface and often become activated after recognizing virus-infected cells. They have diverse antiviral effector functions like the release of cytotoxic granules, cytokine production and antibody dependent cellular cytotoxicity. The importance of NK cell activity in retroviral infections became evident due to the discovery of several viral strategies to escape recognition and elimination by NK cells...
November 8, 2016: Retrovirology
https://www.readbyqxmd.com/read/27814766/antibody-dependent-cd56-t-cell-responses-are-functionally-impaired-in-long-term-hiv-1-infection
#12
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/27795960/immunomodulatory-effects-mediated-by-dopamine
#13
REVIEW
Rodrigo Arreola, Samantha Alvarez-Herrera, Gilberto Pérez-Sánchez, Enrique Becerril-Villanueva, Carlos Cruz-Fuentes, Enrique Octavio Flores-Gutierrez, María Eugenia Garcés-Alvarez, Dora Luz de la Cruz-Aguilera, Emilio Medina-Rivero, Gabriela Hurtado-Alvarado, Saray Quintero-Fabián, Lenin Pavón
Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R)...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27795747/dynamic-analysis-of-immune-and-cancer-cell-interactions-at-single-cell-level-in-microfluidic-droplets
#14
S Sarkar, P Sabhachandani, D Stroopinsky, K Palmer, N Cohen, J Rosenblatt, D Avigan, T Konry
Cell-cell communication mediates immune responses to physiological stimuli at local and systemic levels. Intercellular communication occurs via a direct contact between cells as well as by secretory contact-independent mechanisms. However, there are few existing methods that allow quantitative resolution of contact-dependent and independent cellular processes in a rapid, precisely controlled, and dynamic format. This study utilizes a high-throughput microfluidic droplet array platform to analyze cell-cell interaction and effector functions at single cell level...
September 2016: Biomicrofluidics
https://www.readbyqxmd.com/read/27793919/cell-surface-antibody-retention-influences-in-vivo-antitumor-activity-mediated-by-antibody-dependent-cellular-cytotoxicity
#15
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/27787618/immunogenicity-of-human-embryonic-stem-cell-derived-beta-cells
#16
Cornelis R van der Torren, Arnaud Zaldumbide, Gaby Duinkerken, Simone H Brand-Schaaf, Mark Peakman, Geert Stangé, Laura Martinson, Evert Kroon, Eugene P Brandon, Daniel Pipeleers, Bart O Roep
AIMS/HYPOTHESIS: To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells. METHODS: We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice...
October 27, 2016: Diabetologia
https://www.readbyqxmd.com/read/27777574/phenotypic-and-functional-dysregulated-blood-nk-cells-in-colorectal-cancer-patients-can-be-activated-by-cetuximab-plus-il-2%C3%A2-or-il-15
#17
Yamila Sol Rocca, María Paula Roberti, Estefanía Paula Juliá, María Betina Pampena, Luisina Bruno, Sergio Rivero, Eduardo Huertas, Fernando Sánchez Loria, Alejandro Pairola, Anne Caignard, José Mordoh, Estrella Mariel Levy
The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression...
2016: Frontiers in Immunology
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...
November 21, 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/27757041/infliximab-enhances-the-therapeutic-effects-of-5-fluorouracil-resulting-in-tumor-regression-in-colon-cancer
#20
Fen Liu, Feiyan Ai, Li Tian, Shaojun Liu, Lian Zhao, Xiaoyan Wang
Colon cancer (CC) is among the most common malignant diseases with a dismal survival. Tumor necrosis factor-alpha (TNF-α) has been identified as a therapeutic target in various cancers, and anti-TNF-α treatment has shown promising effects in different cancer models. However, if TNF-α can be targeted in CC, the therapeutic values of anti-TNF-α treatment in CC remain unknown. Our study indicated that TNF-α is highly expressed in CC cell lines and patient tumor samples. High expression of TNF-α is an independent adverse prognosticator of CC...
2016: OncoTargets and Therapy
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