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Antibody dependent cellular cytotoxicity

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https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#1
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28427948/comprehensive-characterization-of-humoral-correlates-of-human-immunodeficiency-virus-1-superinfection-acquisition-in-high-risk-kenyan-women
#2
Keshet Ronen, Adam S Dingens, Susan M Graham, Walter Jaoko, Kishor Mandaliya, R Scott McClelland, Julie Overbaugh
HIV-1 superinfection, in which an infected individual acquires a second HIV-1 infection from a different partner, is one of the only settings in which HIV acquisition occurs in the context of a pre-existing immune response to natural HIV infection. There is evidence that initial infection provides some protection from superinfection, particularly after 6months of initial infection, when development of broad immunity occurs. Comparison of the immune response of superinfected individuals at the time of superinfection acquisition to that of individuals who remain singly infected despite continued exposure can shed light on immune correlates of HIV acquisition to inform prophylactic vaccine design...
April 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28415689/targeting-cd157-in-aml-using-a-novel-fc-engineered-antibody-construct
#3
Christina Krupka, Felix S Lichtenegger, Thomas Köhnke, Jan Bögeholz, Veit Bücklein, Michael Roiss, Torben Altmann, To Uyen Do, Rachel Dusek, Keith Wilson, Arnima Bisht, Jon Terrett, Dee Aud, Esteban Pombo-Villar, Christian Rohlff, Wolfgang Hiddemann, Marion Subklewe
Antibody-based immunotherapy represents a promising strategy to eliminate chemorefractory leukemic cells in acute myeloid leukemia (AML). In this study, we evaluated a novel Fc-engineered antibody against CD157 (MEN1112) for its suitability as immunotherapy in AML. CD157 was expressed in 97% of primary AML patient samples. A significant, albeit lower expression level of CD157 was observed within the compartment of leukemia-initiating cells, which are supposed to be the major source of relapse. In healthy donor bone marrow, CD157 was expressed on CD34+ cells...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405525/obinutuzumab-mediated-high-affinity-ligation-of-fc%C3%AE-riiia-cd16-primes-nk-cells-for-ifn%C3%AE-production
#4
Cristina Capuano, Chiara Pighi, Rosa Molfetta, Rossella Paolini, Simone Battella, Gabriella Palmieri, Giuseppe Giannini, Francesca Belardinilli, Angela Santoni, Ricciarda Galandrini
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), based on the recognition of IgG-opsonized targets by the low-affinity receptor for IgG FcγRIIIA/CD16, represents one of the main mechanisms by which therapeutic antibodies (mAbs) mediate their antitumor effects. Besides ADCC, CD16 ligation also results in cytokine production, in particular, NK-derived IFNγ is endowed with a well-recognized role in the shaping of adaptive immune responses. Obinutuzumab is a glycoengineered anti-CD20 mAb with a modified crystallizable fragment (Fc) domain designed to increase the affinity for CD16 and consequently the killing of mAb-opsonized targets...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404636/antibody-distance-from-the-cell-membrane-regulates-antibody-effector-mechanisms
#5
Kirstie L S Cleary, H T Claude Chan, Sonja James, Martin J Glennie, Mark S Cragg
Immunotherapy using mAbs, such as rituximab, is an established means of treating hematological malignancies. Abs can elicit a number of mechanisms to delete target cells, including complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity, and Ab-dependent cellular phagocytosis. The inherent properties of the target molecule help to define which of these mechanisms are more important for efficacy. However, it is often unclear why mAb binding to different epitopes within the same target elicits different levels of therapeutic activity...
April 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28404572/an-hiv-envelope-gp120-fc-fusion-protein-elicits-effector-antibody-responses-in-rhesus-macaques
#6
Zhanna Shubin, Weizhong Li, Bhawna Poonia, Guido Ferrari, Celia LaBranche, David Montefiori, Xiaoping Zhu, C David Pauza
A goal for HIV prevention programs is to develop safe and effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization or glycosylation of gp120 to activate appropriate germline B cells and mimic the subsequent maturation pathways seen in infected individuals...
April 12, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28402253/immunoregulatory-role-of-b-lymphocytes-in-alloresponse-to-kidney-transplant
#7
Tomasz Baran, Maria Boratyńska
B cells are a group of diverse phenotype and function subsets, which can both stimulate and inhibit the immune response to an allograft. They participate in the rejection process by influencing differentiation, proliferation and effector functions of T lymphocytes. B cells injure the graft via the ADCC (antibody-dependent cellular cytotoxicity) reaction and humoral rejection through plasmocyte production of donor-specific antibodies. A converse, suppressive mode of B cells can attribute to the development of tolerance and protect the graft from rejection...
April 12, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28400633/new-targeted-treatments-for-cutaneous-t-cell-lymphomas
#8
Martine Bagot
Cutaneous T-cell lymphomas (CTCLs) represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath) is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections...
March 2017: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/28397880/glycoengineering-of-pertuzumab-and-its-impact-on-the-pharmacokinetic-pharmacodynamic-properties
#9
Cheng Luo, Song Chen, Na Xu, Chi Wang, Wen Bo Sai, Wei Zhao, Ying Chun Li, Xiao Jing Hu, Hong Tian, Xiang Dong Gao, Wen Bing Yao
Pertuzumab is an antihuman HER2 antibody developed for HER2 positive breast cancer. Glycosylation profiles are always the important issue for antibody based therapy. Previous findings have suggested the impact of glycosylation profiles on the function of antibodies, like pharmacodynamics, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the roles of fucose and sialic acid in the function of therapeutic antibodies still need further investigation, especially the role of sialic acid in nonfucosylated antibodies...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28393238/modulation-of-interactions-of-neuroblastoma-cell-lines-with-extracellular-matrix-proteins-affects-their-sensitivity-to-treatment-with-the-anti-gd2-ganglioside-antibody-14g2a
#10
Irena Horwacik, Hanna Rokita
Children diagnosed with high risk neuroblastoma have poor prognosis which stimulates efforts to broaden therapies of the neoplasm. GD2-ganglioside (GD2) marks neuroblastoma cells and is a target for monoclonal antibodies. We have recently shown that some neuroblastoma cell lines are sensitive to direct cytotoxicity of the anti-GD2 mouse monoclonal antibody 14G2a (mAb). For IMR-32 and LA-N-1 cell lines, treatment with the 14G2a mAb induced evident changes in appearance such as cell rounding, aggregation, loose contact with culture plastic, or detachment...
April 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28387358/corrigendum-cd16-is-indispensable-for-antibody-dependent-cellular-cytotoxicity-by-human-monocytes
#11
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
No abstract text is available yet for this article.
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28375048/arabinosylation-of-recombinant-human-immunoglobulin-based-protein-therapeutics
#12
Patrick Hossler, Christopher Chumsae, Christopher Racicot, David Ouellette, Alexander Ibraghimov, Daniel Serna, Alessandro Mora, Sean McDermott, Boris Labkovsky, Susanne Scesney, Christine Grinnell, Gregory Preston, Sahana Bose, Ralf Carrillo
Protein glycosylation is arguably the paramount post-translational modification on recombinant glycoproteins, and highly cited in the literature for affecting the physiochemical properties and the efficacy of recombinant glycoprotein therapeutics. Glycosylation of human immunoglobulins follows a reasonably well-understood metabolic pathway, which gives rise to a diverse range of asparagine-linked (N-linked), or serine/threonine-linked (O-linked) glycans. In N-linked glycans, fucose levels have been shown to have an inverse relationship with the degree of antibody-dependent cell-mediated cytotoxicity, and high mannose levels have been implicated in potentially increasing immunogenicity and contributing to less favorable pharmacokinetic profiles...
February 17, 2017: MAbs
https://www.readbyqxmd.com/read/28366604/single-n277a-substitution-in-c2-of-simian-immunodeficiency-virus-envelope-influences-vaccine-elicited-cd4i-neutralizing-and-anti-v2-antibody-responses
#13
Xian Tang, Jia Guo, Lin Cheng, Caijun Sun, Li Liu, Teng Zuo, Hui Wang, Ling Chen, Linqi Zhang, Zhiwei Chen
An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified. Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells. Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals. We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28361123/tocilizumab-anti-il-6r-suppressed-tnf%C3%AE-production-by-human-monocytes-in-an-in-vitro-model-of-anti-hla-antibody-induced-antibody-dependent-cellular-cytotoxicity
#14
Bong-Ha Shin, Shili Ge, James Mirocha, Stanley C Jordan, Mieko Toyoda
BACKGROUND: We previously demonstrated that natural killer (NK) cells activated via FcγRIIIa (CD16) interactions with anti-HLA antibodies binding to peripheral blood mononuclear cells (PBMCs) in the in vitro antibody-dependent cellular cytotoxicity (ADCC) assay produced IFNγ. Here we investigate if other CD16 bearing cells are responsive to alloantigen via alloantibody in the in vitro ADCC and if the ADCC-induced cytokine reactions and cytotoxicity can be modified by the anti-interleukin 6 receptor (IL-6R) monoclonal antibody, Tocilizumab (TCZ)...
March 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28358050/antibody-dependent-cellular-cytotoxicity-inducing-antibodies-significantly-affect-the-post-exposure-treatment-of-ebola-virus-infection
#15
Qiang Liu, Changfa Fan, Qianqian Li, Shuya Zhou, Weijin Huang, Lan Wang, Chunyun Sun, Meng Wang, Xi Wu, Jian Ma, Baowen Li, Liangzhi Xie, Youchun Wang
Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28356050/hiv-specific-adcc-new-technologies-to-study-adcc-and-importance-for-the-hiv-vaccine-field
#16
Bruce D Wines, Hugh Billings, Milla R Mcleand, Stephen J Kent, P Mark Hogarth
There is now intense interest in the role of HIV-specific antibodies and the engagement of FcγR functions in the control and prevention of HIV infection. The RV144 vaccine study, natural progression cohorts, and macaque studies all point to a role for antibody dependent cellular cytotoxicity (ADCC) in the control of HIV. However, reliable assays that can be reproducibly used across different laboratories to measure ADCC and other Fc-dependent functions of antibodies are limited. We recently developed a novel ELISA-based assay to detect the binding of viral antigen-specific antibodies to the ectodomains of homo-dimeric Fcγ receptors...
March 28, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28346319/effect-of-combination-antiretroviral-therapy-on-hiv-1-specific-antibody-dependent-cellular-cytotoxicity-responses-in-subtype-b-and-subtype-c-infected-cohorts
#17
Vijaya Madhavi, Archana Kulkarni, Ashwini Shete, Wen Shi Lee, Milla R Mclean, Anne B Kristensen, Manisha Ghate, Bruce D Wines, P Mark Hogarth, Matthew S Parsons, Anthony Kelleher, David A Cooper, Janaki Amin, Sean Emery, Madhuri Thakar, Stephen J Kent
BACKGROUND: There is growing interest in immune therapies to clear the latent HIV-1 after combination antiretroviral therapy (cART). There is limited information on the effect of cART on antibody-dependent cellular cytotoxicity (ADCC) and no studies have directly compared ADCC in HIV-1 subtype B- and subtype C-infected subjects. The effect of improving immunocompetence on ADCC to influenza also remains unexplored. METHODS: The effect of cART on HIV-1- and influenza-specific ADCC was analyzed in two cohorts (39 subtype B- and 47 subtype C-infected subjects) before and after two years of cART...
March 23, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28332900/fc-or-not-fc-that-is-the-question-antibody-fc-receptor-interactions-are-key-to-universal-influenza-vaccine-design
#18
Sinthujan Jegaskanda, Hillary A Vanderven, Adam K Wheatley, Stephen J Kent
A universal vaccine that provides long-lasting protection from both epidemic and pandemic influenza viruses remains the "holy grail" of influenza vaccine research. Though virus neutralization assays are the current benchmark of measuring vaccine effectiveness, it is clear that Fc-receptor functions can drastically improve the effectiveness of antibodies and vaccines in vivo. Antibodies that kill virus-infected cells and/or elicit an antiviral environment, termed antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, provide a link between the innate and adaptive immune response...
March 23, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#19
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28331088/bst-2-expression-modulates-small-cd4-mimetic-sensitization-of-hiv-1-infected-cells-to-adcc
#20
Jonathan Richard, Jérémie Prévost, Benjamin von Bredow, Shilei Ding, Nathalie Brassard, Halima Medjahed, Mathieu Coutu, Bruno Melillo, Frédéric Bibollet-Ruche, Beatrice H Hahn, Daniel E Kaufmann, Amos B Smith, Joseph Sodroski, Daniel Sauter, Frank Kirchhoff, Katrina Gee, Stuart J Neil, David T Evans, Andrés Finzi
Antibodies recognizing conserved CD4-induced (CD4i) epitopes on HIV-1 Env and able to mediate antibody-dependent cellular cytotoxicity (ADCC) have been shown to be present in sera from most HIV-1-infected individuals. These antibodies preferentially recognize Env in its CD4-bound conformation. CD4 downregulation by Nef and Vpu dramatically reduces exposure of CD4i HIV-1 Env epitopes and therefore reduce the susceptibility of HIV-1-infected cells to ADCC mediated by HIV+ sera. Importantly, this mechanism of immune evasion can be circumvented with small-molecule CD4-mimetics (CD4mc) which are able to transition Env into the CD4-bound conformation and sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera...
March 22, 2017: Journal of Virology
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