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Antibody dependent cellular cytotoxicity

Beate Hintersteiner, Nico Lingg, Evelyne Janzek, Oliver Mutschlechner, Hans Loibner, Alois Jungbauer
It has previously been shown for individual antibodies, that the microheterogenity pattern can have a significant impact on various key characteristics of the product. The aim of this study to get a more generalized understanding of the importance of microheterogeneity. For that purpose, the charge variant pattern of various different commercially available therapeutic mAb products was compared using Cation-Exchange Chromatography with linear pH gradient antigen affinity, Fc-receptor affinity, antibody dependent cellular cytotoxicity (ADCC) and conformational stability...
October 18, 2016: Biotechnology Journal
Yong Yu, Jason C H Tsang, Cui Wang, Simon Clare, Juexuan Wang, Xi Chen, Cordelia Brandt, Leanne Kane, Lia S Campos, Liming Lu, Gabrielle T Belz, Andrew N J McKenzie, Sarah A Teichmann, Gordon Dougan, Pentao Liu
Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and are important regulators in immune response and tissue homeostasis(1, 2). ILCs are generated from common lymphoid progenitors (CLPs), which are subsequently committed to innate lymphoid lineages in the α lymphoid progenitor (αLP), early innate lymphoid progenitor (EILP), common helper innate lymphoid progenitor (CHILP) and innate lymphoid cell progenitor (ILCP) compartments(3, 4, 5, 6, 7, 8)...
September 29, 2016: Nature
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
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
Gamze Isitman, Alexandra Tremblay-McLean, Irene Lisovsky, Julie Bruneau, Bertrand Lebouché, Jean-Pierre Routy, Nicole F Bernard
Natural Killer (NK) cell education, which requires the engagement of inhibitory NK cell receptors (iNKRs) by their ligands, is important for generating self-tolerant functional NK cells. While the potency of NK cell education is directly related to their functional potential upon stimulation with HLA null cells, the influence of NK cell education on the potency of the antibody dependent cellular cytotoxicity (ADCC) function of NK cells is unclear. ADCC occurs when the Fc portion of an immunoglobulin G antibody bridges the CD16 Fc receptor on NK cells and antigen on target cells, resulting in NK cell activation, cytotoxic granule release, and target cell lysis...
2016: PloS One
Mengchao Shi, Kristopher A Kleski, Kevin R Trabbic, Jean-Paul Bourgault, Peter R Andreana
Sialyl Tn (STn) is a tumor associated carbohydrate antigen (TACA) that is overexpressed in a variety of carcinomas such as breast, ovarian and colon cancer. In normal tissue, STn is not detectable which is critical for opportunities in develop-ing cancer immunotherapies. A novel, entirely carbohydrate, semi-synthetic STn-PS A1 conjugate was prepared and eval-uated in C57BL/6 mice. STn-PS A1 was combined with commercially available monophosphoryl lipid A (MPL)-based ad-juvant and after immunization, ELISA indicated a strong immune response for inducing both anti-STn IgM/IgG antibod-ies...
October 11, 2016: Journal of the American Chemical Society
Martin R Goodier, Chiara Lusa, Sam Sherratt, Ana Rodriguez-Galan, Ron Behrens, Eleanor M Riley
Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downregulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells in vivo after intramuscular (but not intranasal) influenza vaccination...
2016: Frontiers in Immunology
Dara M Strauss-Albee, Emily C Liang, Thanmayi Ranganath, Natali Aziz, Catherine A Blish
BACKGROUND: Infection is a leading cause of death worldwide in babies under one month of age. Better vaccines and therapeutics are desperately needed for this vulnerable population. METHODS: Because newborns rely heavily on the innate immune system, we evaluated cell phenotype and function of some of the earliest cellular responders during infection, natural killer (NK) cells. We used mass cytometry to provide a comprehensive comparison of NK cells from umbilical cord blood and adult peripheral blood...
October 7, 2016: Cytometry. Part B, Clinical Cytometry
Yosuke Hashimoto, Yumi Kawahigashi, Tomoyuki Hata, Xiangru Li, Akihiro Watari, Minoru Tada, Akiko Ishii-Watabe, Yoshiaki Okada, Takefumi Doi, Masayoshi Fukasawa, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
Claudin-4 (CLDN-4), a tight-junction protein, is overexpressed in various malignant tumors, including gastric, colorectal, pancreatic, and breast cancers. However, CLDN-4 is also expressed in normal tissues, including the liver, pancreas, kidney, and small intestine. Whether CLDN-4 is an effective and safe target for cancer therapy has been unclear owing to the lack of a binder with both CLDN-4 specificity and cross-reactivity to human and murine cells. In this study, we successfully generated a rat anti-CLDN-4 monoclonal antibody (5D12) that was specific to, and cross-reactive with, human and mouse CLDN-4...
October 2016: Pharmacology Research & Perspectives
Li-Chan Yang, Ching-Yi Lai, Wen-Chuan Lin
This study investigated the effects of a type II arabinogalactan from Anoectochilus formosanus (AGAF) on natural killer (NK) cell-mediated cytotoxicity and the possible underlying mechanisms. This study reported that sustained exposure to AGAF increased NK-92MI cell-mediated cytotoxicity in a time- and concentration-dependent manner, as characterized according to the cellular lactic dehydrogenase leakage from K562 leukemia cells. Additionally, antibody neutralization studies have reported that interferon (IFN)-γ, but not perforin or tumor necrosis factor-α, released by NK-92MI NK cells is crucial in enhancing cytotoxicity through an autocrine loop...
January 2, 2017: Carbohydrate Polymers
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
John O Richards, Alex J Albers, Thomas S Smith, Judy A Tjoe
No abstract text is available yet for this article.
October 1, 2016: Cancer Immunology, Immunotherapy: CII
Hermann Einsele, Martin Schreder
Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells...
October 2016: Therapeutic Advances in Hematology
Masayuki Homma, Akiyuki Uzawa, Hitoshi Tanaka, Naoki Kawaguchi, Tetsuya Kanai, Kenji Nakajima, Masakuni Narita, Yukio Hara, Hideya Maruyama, Yasumasa Ogawa, Keiichi Himuro, Satoshi Kuwabara
Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG...
September 27, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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
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
Bai Liu, Lin Kong, Kaiping Han, Hao Hong, Warren D Marcus, Xiaoyue Chen, Emily K Jeng, Sarah Alter, Xiaoyun Zhu, Mark P Rubinstein, Sixiang Shi, Peter R Rhode, Weibo Cai, Hing C Wong
Interleukin (IL)-15 and its receptor α (IL-15Rα) are co-expressed on antigen-presenting cells allowing transpresentation of IL-15 to immune cells bearing IL-2RβγC and stimulation of effector immune responses. We previously reported that the high-affinity interactions between an IL-15 superagonist (IL-15N72D) and the extracellular IL-15Rα sushi domain (IL-15RαSu) could be exploited to create a functional scaffold for the design of multivalent disease-targeted complexes. The IL-15N72D/IL-15RαSuFc complex, also known as ALT-803, is a multimeric complex constructed by fusing IL-15N72D/IL-15RαSu to the Fc-domain of IgG1...
September 20, 2016: Journal of Biological Chemistry
Isaak Quast, Benjamin Peschke, Jan D Lünemann
Immunoglobulin gamma (IgG) antibodies are key effector proteins of the immune system. They recognize antigens with high specificity and are indispensable for immunological memory following pathogen exposure or vaccination. The constant, crystallizable fragment (Fc) of IgG molecules mediates antibody effector functions such as complement-dependent cytotoxicity, antibody-mediated cellular cytotoxicity, and antibody-dependent cell-mediated phagocytosis. These functions are regulated by a single N-linked, biantennary glycan of the heavy chain, which resides just below the hinge region, and the presence of specific sugar moieties on the glycan has profound implications on IgG effector functions...
September 17, 2016: Cellular and Molecular Life Sciences: CMLS
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
Akira Iizuka, Ryota Kondou, Chizu Nonomura, Tadashi Ashizawa, Keiichi Ohshima, Masatoshi Kusuhara, Mitsuhiro Isaka, Yasuhisa Ohde, Ken Yamaguchi, Yasuto Akiyama
Tumor immune regulation has been demonstrated in clinical studies using antibodies targeted to the B7/CD28 family. B7 homolog 4 (B7-H4) negatively regulates immune responses and is overexpressed in many types of human cancer, indicating that B7-H4 may be a potential target of cancer therapy. B7-H4 expression is affected by the microenvironment, and its presence has been reported in cancer tissues and immune cells. We found an upregulation of B7-H4 expression using comprehensive whole exome sequencing and gene expression profiling (project HOPE) launched by the Shizuoka Cancer Center based on tumor tissue samples from 1,058 cancer patients...
September 12, 2016: Oncology Reports
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