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https://www.readbyqxmd.com/read/28448604/non-invasive-imaging-assessment-of-the-biodistribution-of-gsk2849330-an-adcc-and-cdc-optimized-anti-her3-mab-and-its-role-in-tumor-macrophage-recruitment-in-human-tumor-bearing-mice
#1
Hasan Alsaid, Tinamarie Skedzielewski, Mary V Rambo, Kristen Hunsinger, Bao Hoang, William Fieles, Edward R Long, James Tunstead, Danielle J Vugts, Matthew Cleveland, Neil Clarke, Christopher Matheny, Beat M Jucker
The purpose of this work was to use various molecular imaging techniques to non-invasively assess GSK2849330 (anti HER3 ADCC and CDC enhanced 'AccretaMab' monoclonal antibody) pharmacokinetics and pharmacodynamics in human xenograft tumor-bearing mice. Immuno-PET biodistribution imaging of radiolabeled 89Zr-GSK2849330 was assessed in mice with HER3 negative (MIA-PaCa-2) and positive (CHL-1) human xenograft tumors. Dose dependency of GSK2849330 disposition was assessed using varying doses of unlabeled GSK2849330 co-injected with 89Zr-GSK2849330...
2017: PloS One
https://www.readbyqxmd.com/read/28434980/thaw-and-use-target-cells-pre-labeled-with-calcein-am-for-antibody-dependent-cell-mediated-cytotoxicity-assays
#2
Shan Chung, Van Nguyen, Yuwen Linda Lin, Lynn Kamen, An Song
In vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays are routinely performed to support the research and development of therapeutic antibodies. In ADCC assays, target cells bound by the antibodies are lysed by activated effector cells following interactions between the Fc region of the bound antibody and Fcγ receptors on effector cells. Target cell lysis is typically measured by quantification of released endogenous enzymes, e.g., lactate dehydrogenase, or measurement of released exogenous labels, e...
April 20, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#3
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415754/gene-modified-nk-92mi-cells-expressing-a-chimeric-cd16-bb-%C3%AE-or-cd64-bb-%C3%AE-receptor-exhibit-enhanced-cancer-killing-ability-in-combination-with-therapeutic-antibody
#4
Ying Chen, Fengtao You, Licui Jiang, Jialu Li, Xuejun Zhu, Yangyi Bao, Xiang Sun, Xiaowen Tang, Huimin Meng, Gangli An, Bozhen Zhang, Lin Yang
Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually mediates ADCC is absent in NK-92 and NK-92MI cells. To apply NK-92MI cell-based immunotherapy to cancer treatment, we designed and generated two chimeric receptors in NK-92MI cells that can bind the Fc portion of human immunoglobulins...
March 15, 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
#5
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/28405498/cergutuzumab-amunaleukin-cea-il2v-a-cea-targeted-il-2-variant-based-immunocytokine-for-combination-cancer-immunotherapy-overcoming-limitations-of-aldesleukin-and-conventional-il-2-based-immunocytokines
#6
Christian Klein, Inja Waldhauer, Valeria G Nicolini, Anne Freimoser-Grundschober, Tapan Nayak, Danielle J Vugts, Claire Dunn, Marije Bolijn, Jörg Benz, Martine Stihle, Sabine Lang, Michaele Roemmele, Thomas Hofer, Erwin van Puijenbroek, David Wittig, Samuel Moser, Oliver Ast, Peter Brünker, Ingo H Gorr, Sebastian Neumann, Maria Cristina de Vera Mudry, Heather Hinton, Flavio Crameri, Jose Saro, Stefan Evers, Christian Gerdes, Marina Bacac, Guus van Dongen, Ekkehard Moessner, Pablo Umaña
We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA-targeted immunocytokine, that comprises a single IL-2 variant (IL2v) moiety with abolished CD25 binding, fused to the C-terminus of a high affinity, bivalent carcinoembryonic antigen (CEA)-specific antibody devoid of Fc-mediated effector functions. Its molecular design aims to (i) avoid preferential activation of regulatory T-cells vs. immune effector cells by removing CD25 binding; (ii) increase the therapeutic index of IL-2 therapy by (a) preferential retention at the tumor by having a lower dissociation rate from CEA-expressing cancer cells vs...
2017: Oncoimmunology
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/28397880/glycoengineering-of-pertuzumab-and-its-impact-on-the-pharmacokinetic-pharmacodynamic-properties
#8
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/28392901/mutation-analysis-of-connexin-50-gene-among-iranian-families-with-autosomal-dominant-cataracts
#9
Masoumeh Mohebi, Saeed Chenari, Abolfazl Akbari, Fariba Ghassemi, Mehran Zarei-Ghanavati, Ghasem Fakhraie, Nahid Babaie, Mansour Heidari
OBJECTIVES: Childhood cataract is a genetically heterogeneous eye disorder that results in visual impairment. The aim of this study was to identify the genetic mutations of connexin 50 gene among Iranian families suffered from autosomal dominant congenital cataracts (ADCC). MATERIALS AND METHODS: Families, having at least two members with bilateral familial congenital cataract, were selected for the study. Probands were evaluated by detailed ophthalmologist's examination, and the pedigree analysis was performed...
March 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28386362/b7-h3-regulates-migration-and-invasion-in-salivary-gland-adenoid-cystic-carcinoma-via-the-jak2-stat3-signaling-pathway
#10
Teng-Fei Fan, Wei-Wei Deng, Lin-Lin Bu, Tian-Fu Wu, Wen-Feng Zhang, Zhi-Jun Sun
B7 Homolog 3 (B7-H3), a newly identified member of the B7 family, is over-expressed in various human cancers and plays a vital role in tumor progression. To identify the expression pattern of B7-H3 in human salivary adenoid cystic carcinoma (AdCC) and its underlying mechanisms, we characterized B7-H3 expression in AdCC tissue microarrays using immunohistochemical staining, and analyzed potentially associated molecules. The results showed that B7-H3 was highly expressed in salivary AdCC, compared with normal salivary glands...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28377769/antibody-dependent-cell-mediated-cytotoxicity-epitopes-on-the-hemagglutinin-head-region-of-pandemic-h1n1-influenza-virus-play-detrimental-roles-in-h1n1-infected-mice
#11
Zi-Wei Ye, Shuofeng Yuan, Kwok-Man Poon, Lei Wen, Dong Yang, Zehua Sun, Cun Li, Meng Hu, Huiping Shuai, Jie Zhou, Mei-Yun Zhang, Bo-Jian Zheng, Hin Chu, Kwok-Yung Yuen
Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model...
2017: Frontiers in Immunology
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...
May 2017: MAbs
https://www.readbyqxmd.com/read/28370175/expression-of-cancer-testis-antigens-in-salivary-gland-carcinomas-with-reference-to-mage-a-and-ny-eso-1-expression-in-adenoid-cystic-carcinoma
#13
Shintaro Beppu, Yohei Ito, Kana Fujii, Kousuke Saida, Hisashi Takino, Ayako Masaki, Takayuki Murase, Kimihide Kusafuka, Yoshiyuki Iida, Tetsuro Onitsuka, Yasushi Yatabe, Nobuhiro Hanai, Yasuhisa Hasegawa, Kei Ijichi, Shingo Murakami, Hiroshi Inagaki
BACKGROUND: Salivary gland carcinomas comprise a group of heterogeneous lesions with complex clinicopathological characteristics and distinct biological behaviors. However, recurrent or metastatic tumors are difficult to treat with currently available therapies. Cancer-testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. CTAs are highly immunogenic proteins and thus represent ideal targets for cytotoxic T-lymphocyte-mediated specific immune therapy...
March 28, 2017: Histopathology
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
#14
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
#15
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
#16
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/28356526/chimeric-hemagglutinin-constructs-induce-broad-protection-against-influenza-b-virus-challenge-in-the-mouse-model
#17
Megan Ermler, Ericka Kirkpatrick, Weina Sun, Rong Hai, Fatima Amanat, Veronika Chromikova, Peter Palese, Florian Krammer
Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses...
March 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28356050/hiv-specific-adcc-new-technologies-to-study-adcc-and-importance-for-the-hiv-vaccine-field
#18
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
#19
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/28337279/agr2-promotes-the-proliferation-migration-and-regulates-epithelial-mesenchymal-transition-in-salivary-adenoid-cystic-carcinoma
#20
Si-Rui Ma, Liang Mao, Wei-Wei Deng, Yi-Cun Li, Lin-Lin Bu, Guang-Tao Yu, Wen-Feng Zhang, Zhi-Jun Sun
Salivary adenoid cystic carcinoma (AdCC) is a common head and neck cancer with the propensity for local spread and distant metastasis. In our previous study, elevated expression of Anterior gradient 2 (AGR2) was detected in head and neck squamous cell carcinoma (HNSCC), associated with epithelial-mesenchymal transition (EMT) and cancer stemness. However, to date, the expression and function of AGR2 in AdCC has yet to be elucidated. In the present study, human AdCC tissue microarrays including 18 cases of normal salivary gland (NSG), 12 cases of pleomorphic adenoma (PMA) and 72 cases of AdCC were employed for immunohistochemical staining analysis...
2017: American Journal of Translational Research
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