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https://www.readbyqxmd.com/read/28088123/antibody-dependent-cellular-cytotoxicity-and-influenza-virus
#1
REVIEW
Hillary A Vanderven, Sinthujan Jegaskanda, Adam K Wheatley, Stephen J Kent
Antibodies are a key defence against influenza infection and disease, but neutralizing antibodies are often strain-specific and of limited utility against divergent or pandemic viruses. There is now considerable evidence that influenza-specific antibodies with Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can assist in the clearance of influenza infection in vitro and in animal models. Further, ADCC-mediating antibodies that recognize a broad array of influenza strains are common in humans, likely as a result of being regularly exposed to influenza infections...
January 11, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28087106/charge-variant-analysis-of-proposed-biosimilar-to-trastuzumab
#2
Pravinkumar Dakshinamurthy, Pavithra Mukunda, Bhargav Prasad Kodaganti, Bharath Ravindra Shenoy, Bairavabalakumar Natarajan, Amol Maliwalave, Vivek Halan, Sathyabalan Murugesan, Sunit Maity
Trastuzumab is a humanized monoclonal antibody (mAb) employed for the treatment of HER2 Positive Breast Cancer. A HER2 overexpressing tumor cell binds to Trastuzumab and attracts immune cells which lead to induction of Antibody Dependent Cellular Cytotoxicity (ADCC) by binding to Fc receptors (CD16a or FcγRIIIa) on an effector cell, such as natural killer (NK) cells. The most commonly expressed receptor on NK cell is CD16a which binds to the Fc portion of Trastuzumab. The ligand-independent HER2-HER3 dimerization is the most potent stimulator of downstream pathways for regulation of cell growth and survival...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28077575/effector-attenuating-substitutions-that-maintain-antibody-stability-and-reduce-toxicity-in-mice
#3
Megan Lo, Hok Seon Kim, Raymond K Tong, Travis W Bainbridge, Jean-Michel Vernes, Yin Zhang, Yuwen Linda Lin, Shan Chung, Mark S Dennis, Y Joy Yu Zuchero, Ryan J Watts, Jessica A Couch, Y Gloria Meng, Jasvinder K Atwal, Randall J Brezski, Christoph Spiess, James A Ernst
The antibody Fc region regulates antibody cytotoxic activities and serum half-life. In a therapeutic context however, the cytotoxic effector function of an antibody is often not desirable and can create safety liabilities by activating native host immune defenses against cells expressing the receptor-antigens. Several amino acid changes in the Fc region have been reported to silence or reduce the effector function of antibodies. These earlier studies focused primarily on the interaction of human antibodies with human Fc-Gamma; receptors, and it remains largely unknown how such changes to the Fc might translate in the context of a murine antibody...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069361/dna-mva-protein-vaccination-of-rhesus-macaques-induces-hiv-specific-immunity-in-mucosal-associated-lymph-nodes-and-functional-antibodies
#4
Gerald K Chege, Wendy A Burgers, Tracey L Müller, Clive M Gray, Enid G Shephard, Susan W Barnett, Guido Ferrari, David Montefiori, Carolyn Williamson, Anna-Lise Williamson
Successful future HIV vaccines are expected to generate an effective cellular and humoral response against the virus in both the peripheral blood and mucosal compartments. We previously reported the development of DNA-C and MVA-C vaccines based on HIV-1 subtype C and demonstrated their immunogenicity when given in a DNA prime-MVA boost combination in a nonhuman primate model. In the current study, rhesus macaques previously vaccinated with a DNA-C and MVA-C vaccine regimen were re-vaccinated 3.5years later with MVA-C followed by a protein vaccine based on HIV-1 subtype C envelope formulated with MF59 adjuvant (gp140Env/MF59), and finally a concurrent boost with both vaccines...
January 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28060015/ifn-%C3%AE-augments-nk-mediated-antibody-dependent-cellular-cytotoxicity-adcc-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-mhc-i-downregulation
#5
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct NK cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon MHC-I downregulation capacity. Here, we investigated if Antibody Dependent Cellular Cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α pre-stimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1 infected subjects (ART-suppressed or Elite Controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1 infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28057542/an-fc-silenced-igg1-format-with-extended-half-life-designed-for-improved-stability
#6
M Jack Borrok, Neil Mody, Xiaojun Lu, Megan Kuhn, Herren Wu, William F Dall'Acqua, Ping Tsui
Multiple mutation combinations in the IgG Fc have been characterized to tailor immune effector function or IgG serum persistence to fit desired biological outcomes for monoclonal antibody therapeutics. An unintended consequence of introducing mutations in the Fc (particularly the CH2 domain) can be a reduction in biophysical stability which can correlate with increased aggregation propensity, poor manufacturability, and lower solubility. Herein, we characterize the changes in IgG conformational and colloidal stability when two sets of CH2 mutations "TM" (L234F/L235E/P331S) and "YTE" (M252Y/S254T/T256E) are combined to generate an antibody format lacking immune receptor binding and exhibiting extended half-life...
January 2, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28031227/cetuximab-resistance-in-head-and-neck-cancer-is-mediated-by-egfr-k521-polymorphism
#7
Friederike Braig, Malte Kriegs, Beate Habel, Minna Voigtlaender, Tobias Grob, Karina Biskup, Véronique Blanchard, Markus Sack, Anja Thalhammer, Isabel Ben Batalla, Ingke Braren, Simon Laban, Antje Danielczyk, Steffen Goletz, Elzbieta Jakubowicz, Bruno Märkl, Martin Trepel, Rainald Knecht, Kristoffer Riecken, Boris Fehse, Sonja Loges, Carsten Bokemeyer, Mascha Binder
Head and neck squamous cell carcinomas (HNSCC) exhibiting resistance to the EGFR targeting drug cetuximab poses a challenge to their effective clinical management. Here we report a specific mechanism of resistance in this setting based upon the presence of a single nucleotide polymorphism encoding EGFR-K521 (K-allele), which is expressed in >40% of HNSCC cases. Patients expressing the K-allele showed significantly shorter progression-free survival upon palliative treatment with cetuximab plus chemotherapy or radiation...
December 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/28029136/application-of-lectin-array-technology-for-biobetter-characterization-its-correlation-with-fc%C3%AE-riii-binding-and-adcc
#8
Markus Roucka, Klaus Zimmermann, Markus Fido, Andreas Nechansky
Lectin microarray technology was applied to compare the glycosylation pattern of the monoclonal antibody MB311 expressed in SP2.0 cells to an antibody-dependent cellular cytotoxic effector function (ADCC)-optimized variant (MB314). MB314 was generated by a plant expression system that uses genetically modified moss protoplasts (Physcomitrella patens) to generate a de-fucosylated version of MB311. In contrast to MB311, no or very low interactions of MB314 with lectins Aspergillus oryzae l-fucose (AOL), Pisum sativum agglutinin (PSA), Lens culinaris agglutinin (LCA), and Aleuria aurantia lectin (AAL) were observed...
December 24, 2016: Microarrays
https://www.readbyqxmd.com/read/28027665/three-year-durability-of-immune-responses-induced-by-hiv-dna-and-hiv-modified-vaccinia-virus-ankara-and-effect-of-a-late-hiv-mva-boost-in-tanzanian-volunteers
#9
Agricola Joachim, Patricia J Munseri, Charlotta Nilsson, Muhammad Bakari, Said Aboud, Eligius F Lyamuya, Teghesti Tecleab, Valentina Liakina, Gabriella Scarlatti, Merlin Robb, Patricia Earl, Bernard Moss, Britta Wahren, Fred Mhalu, Guido Ferarri, Eric Sandström, Gunnel Biberfeld
We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization three years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100)...
December 27, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28025620/a-novel-crybb2-stopgain-mutation-causing-congenital-autosomal-dominant-cataract-in-a-chinese-family
#10
Yu Zhou, Yaru Zhai, Lulin Huang, Bo Gong, Jie Li, Fang Hao, Zhengzheng Wu, Yi Shi, Yin Yang
Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples...
2016: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28011910/human-seasonal-influenza-a-viruses-induce-h7n9-cross-reactive-antibody-dependent-cellular-cytotoxicity-adcc-antibodies-that-are-directed-towards-the-nucleoprotein
#11
Sinthujan Jegaskanda, Mary Dawn T Co, John Cruz, Kanta Subbarao, Francis A Ennis, Masanori Terajima
Antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) against avian influenza virus subtypes including H7N9 and H5N1 have been detected in human sera. There are limited data on the presence of such cross-reactive ADCC mediating antibodies (ADCC-Abs) in children and the viral target(s) of these Abs are poorly understood. Using high-throughput NK cell activation and NK cytotoxicity assays, we compared ADCC-Abs in sera collected from healthy infants (≤1 year), children (2-17 years) and adults (≥18 years) against H7N9 virus-infected cells and recombinant HA, NA and NP proteins...
December 23, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28009988/a-neutralized-human-lmp1-igg-inhibits-enktl-growth-by-suppressing-the-jak3-stat3-signaling-pathway
#12
Yuan Mao, Jun Wang, Mingzhi Zhang, Weifei Fan, Qi Tang, Siping Xiong, Xiaojun Tang, Juqing Xu, Lin Wang, Shu Yang, Suyao Liu, Li Xu, Yan Chen, Lin Xu, Rong Yin, Jin Zhu
Latent membrane protein 1 (LMP1), which is associated with the development of different types of Epstein-Barr virus (EBV) related lymphoma, has been suggested to be an important oncoprotein. In this study, a human anti-LMP1 IgG antibody (LMP1-IgG) was constructed and characterized by ELISA, western blotting (WB), affinity and immunohistochemistry (IHC) analyses. CCK-8, MTT, apoptosis assays, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of LMP1-IgG on extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTL)...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28009435/anti-cd22-and-anti-cd79b-antibody-drug-conjugates-preferentially-target-proliferating-b-cells
#13
Franklin K Fuh, Caroline Looney, Dongwei Li, Kirsten A Poon, Randall C Dere, Dimitry M Danilenko, Jacqueline McBride, Chae Reed, Shan Chung, Bing Zheng, William R Mathews, Andrew Polson, Saileta Prabhu, Marna Williams
BACKGROUND AND PURPOSE: CD22 and CD79b are cell-surface receptors expressed on B-cell-derived malignancies such as non-Hodgkin's lymphoma (NHL). An anti-mitotic agent monomethyl auristatin E was conjugated to anti-CD22 and anti-CD79b antibodies to develop target-specific therapies for NHL. The mechanism of action (MOA) and pharmacologic and pharmacokinetic (PK) profiles of these antibody-drug conjugates (ADCs) were investigated in cynomolgus monkeys. EXPERIMENTAL APPROACH: Animals were administered anti-CD22 or anti-CD79b ADCs, respective unconjugated antibodies, or vehicle...
December 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28004383/a-real-time-digital-bio-imaging-system-to-quantify-cellular-cytotoxicity-as-an-alternative-to-the-standard-chromium-51-release-assay
#14
Julien Fassy, Kyriaki Tsalkitzi, Emie Salavagione, Nedra Hamouda-Tekaya, Véronique M Braud
Reliable measurement of cellular cytotoxicity is essential for the characterization of immune responses and for the monitoring of antibody treatment efficacy. Until now, the standard chromium ((51) Cr) release assay has remained the sole sensitive assay that measures cellular cytotoxicity. Alternative non-radioactive assays have been developed but they do not provide accurate measurement of target cell cytotoxicity. The cost and hazard of handling radioactivity are strong incentive to find alternative solutions to (51) Cr...
December 22, 2016: Immunology
https://www.readbyqxmd.com/read/27999754/neuroblastoma-patients-with-high-affinity-fcgr2a-3a-and-stimulatory-kir-2ds2-treated-by-long-term-infusion-of-anti-gd2-antibody-ch14-18-cho-show-higher-adcc-levels-and-improved-event-free-survival
#15
Nikolai Siebert, Christian Jensen, Sascha Troschke-Meurer, Maxi Zumpe, Madlen Jüttner, Karoline Ehlert, Silke Kietz, Ina Müller, Holger N Lode
Polymorphisms in Fc-gamma-receptor (FCGR) genes as well as killer cell immunoglobulin-like receptor (KIR) and KIR ligand (KIRL) repertoires may influence antitumor effects of monoclonal antibodies (mAb). Here, we systematically analyzed high- and low-affinity FCGR2A and -3A genotypes as well as stimulating and inhibitory KIR/KIRL combinations in 53 neuroblastoma (NB) patients treated by long-term infusion (LTI) of anti-GD2 IgG1 Ab ch14.18/CHO using validated real-time PCR methods. Patients with high-affinity FCGR2A and -3A genotypes showed a higher level of Ab-dependent cell-mediated cytotoxicity (ADCC) on day 8 after the start of ch14...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27994063/biological-characterization-of-a-stable-effector-functionless-sefl-monoclonal-antibody-scaffold-in-vitro
#16
Ling Liu, Frederick W Jacobsen, Nancy Everds, Yao Zhuang, Yan Bin Yu, Nianyu Li, Darcey Clark, Mai Phuong Nguyen, Madeline Fort, Padma Narayanan, Kei Kim, Riki Stevenson, Linda Narhi, Kannan Gunasekaran, Jeanine L Bussiere
The Stable Effector FunctionLess (SEFL) antibody was designed as an IgG1 antibody with a constant region that lacks the ability to interact with Fcγ receptors. The engineering and stability and pharmacokinetic assessments of the SEFL scaffold is described in the accompanying article titled "Engineering an IgG Scaffold Lacking Effector Function with Optimized Developability" by Jacobsen et al. The biological properties of these SEFL antibodies were assessed in a variety of human and cynomolgus monkey in vitro assays...
December 19, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27974718/c-myb-overexpression-in-cytology-smears-of-tracheobronchial-and-pulmonary-adenoid-cystic-carcinomas
#17
Archana George Vallonthaiel, Deepali Jain, Varsha Singh, Kavneet Kaur, Karan Madan, Vinay Kumar, Venkateswaran K Iyer, Mehar Chand Sharma
AIMS: Adenoid cystic carcinoma (AdCC) is a malignant epithelial neoplasm that occurs rarely in the lower respiratory tract (LRT). AdCC at various sites is associated with the novel fusion transcript MYB-NFIB, along with the overexpression of the Myb protein. The expression of the Myb protein in AdCC of the LRT has not been evaluated much. STUDY DESIGN: Cases of AdCC of the LRT diagnosed on cytology or histology were retrieved from our institutional archives. c-Myb expression was analyzed on immunocytochemistry/immunohistochemistry (ICC/IHC) and was correlated with clinicopathological parameters...
December 15, 2016: Acta Cytologica
https://www.readbyqxmd.com/read/27942585/tissue-memory-b-cell-repertoire-analysis-after-alvac-aidsvax-b-e-gp120-immunization-of-rhesus-macaques
#18
Kan Luo, Hua-Xin Liao, Ruijun Zhang, David Easterhoff, Kevin Wiehe, Thaddeus C Gurley, Lawrence C Armand, Ashley A Allen, Tarra A Von Holle, Dawn J Marshall, John F Whitesides, Jamie Pritchett, Andrew Foulger, Giovanna Hernandez, Robert Parks, Krissey E Lloyd, Christina Stolarchuk, Sheetal Sawant, Jessica Peel, Nicole L Yates, Erika Dunford, Sabrina Arora, Amy Wang, Cindy M Bowman, Laura L Sutherland, Richard M Scearce, Shi-Mao Xia, Mattia Bonsignori, Justin Pollara, R Whitney Edwards, Sampa Santra, Norman L Letvin, James Tartaglia, Donald Francis, Faruk Sinangil, Carter Lee, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Nelson L Michael, Jerome H Kim, S Munir Alam, Nathan A Vandergrift, Guido Ferrari, David C Montefiori, Georgia D Tomaras, Barton F Haynes, M Anthony Moody
The ALVAC prime/ALVAC + AIDSVAX B/E boost RV144 vaccine trial induced an estimated 31% efficacy in a low-risk cohort where HIV‑1 exposures were likely at mucosal surfaces. An immune correlates study demonstrated that antibodies targeting the V2 region and in a secondary analysis antibody-dependent cellular cytotoxicity (ADCC), in the presence of low envelope-specific (Env-specific) IgA, correlated with decreased risk of infection. Thus, understanding the B cell repertoires induced by this vaccine in systemic and mucosal compartments are key to understanding the potential protective mechanisms of this vaccine regimen...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27939300/characterization-of-fc%C3%AE-riiia-effector-cells-used-in-in-vitro-adcc-bioassay-comparison-of-primary-nk-cells-with-engineered-nk-92-and-jurkat-t-cells
#19
Yao-Te Hsieh, Poonam Aggarwal, David Cirelli, Ling Gu, Teresa Surowy, Ned M Mozier
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important mechanism of action (MOA) of several therapeutic antibody drugs and evaluation in ADCC bioassays is important in antibody drug development and maintenance. Three types of effector cells now routinely used in bioassay evaluation of ADCC are natural killer cells from human donors (FcγRIIIA+primary NK), FcγRIIIA engineered NK-92 cells and FcγRIIIA/NFAT-RE/luc2 engineered Jurkat T cells. Engineered effector cells were developed to address need for improved precision and accuracy of classic NK cell ADCC bioassays...
December 8, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27923642/development-of-ifn-%C3%AE-secretory-elispot-based-assay-for-screening-of-adcc-responses
#20
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 elicited by plasma samples of 23 HIV infected individuals against Env and Gag peptides using granulocytes as antigen presenting cells were assessed by both the methods...
December 5, 2016: Journal of Immunological Methods
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