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Antibody dependent cellular cytotoxicity

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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/28074864/a-novel-monoclonal-antibody-targeting-coxsackie-virus-and-adenovirus-receptor-inhibits-tumor-growth-in-vivo
#3
Manabu Kawada, Hiroyuki Inoue, Masunori Kajikawa, Masahito Sugiura, Shuichi Sakamoto, Sakiko Urano, Chigusa Karasawa, Ihomi Usami, Mitsuru Futakuchi, Tohru Masuda
To create a new anti-tumor antibody, we conducted signal sequence trap by retrovirus-meditated expression method and identified coxsackie virus and adenovirus receptor (CXADR) as an appropriate target. We developed monoclonal antibodies against human CXADR and found that one antibody (6G10A) significantly inhibited the growth of subcutaneous as well as orthotopic xenografts of human prostate cancer cells in vivo. Furthermore, 6G10A also inhibited other cancer xenografts expressing CXADR, such as pancreatic and colorectal cancer cells...
January 11, 2017: Scientific Reports
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
#4
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/28031227/cetuximab-resistance-in-head-and-neck-cancer-is-mediated-by-egfr-k521-polymorphism
#5
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
#6
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
#7
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/28018347/advances-in-therapeutic-fc-engineering-modulation-of-igg-associated-effector-functions-and-serum-half-life
#8
REVIEW
Abhishek Saxena, Donghui Wu
Today, monoclonal immunoglobulin gamma (IgG) antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs) is achieved through both its antigen-binding fragment (Fab) and crystallizable fragment (Fc). Fab can specifically recognize tumor-associated antigen (TAA) and thus modulate TAA-linked downstream signaling pathways that may lead to the inhibition of tumor growth, induction of tumor apoptosis, and differentiation...
2016: Frontiers in Immunology
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
#9
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/28009435/anti-cd22-and-anti-cd79b-antibody-drug-conjugates-preferentially-target-proliferating-b-cells
#10
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
#11
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/27956345/intelligent-substance-delivery-into-cells-using-cell-penetrating-peptides
#12
REVIEW
Toshihiko Tashima
Cell-penetrating peptides (CPPs) are oligopeptides that can permeate the cell membrane. The use of a CPP-mediated transport system could be an excellent method for delivering cell-impermeable substances such as proteins, antibodies, antisense oligonucleotides, siRNAs, plasmids, drugs, fluorescent compounds, and nanoparticles as covalently or noncovalently conjugated cargo into cells. Nonetheless, the mechanisms through which CPPs are internalized remain unclear. Endocytosis and direct translocation through the membrane are the generally accepted routes...
January 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27943633/integrated-genome-and-protein-editing-swaps-%C3%AE-2-6-sialylation-for-%C3%AE-2-3-sialic-acid-on-recombinant-antibodies-from-cho
#13
Cheng-Yu Chung, Qiong Wang, Shuang Yang, Bojiao Yin, Hui Zhang, Michael Betenbaugh
Immunoglobin G with α-2,6 sialylation has been reported to have an impact on antibody-depend cellular cytotoxicity and anti-inflammatory efficacy. However, production of antibodies with α-2,6 sialylation from Chinese hamster ovary cells is challenging due to the inaccessibility of sialyltransferases for the heavy chain N-glycan site and the presence of exclusively α-2,3 sialyltransferases. In this study, combining mutations on the Fc regions to allow sialyltransferase accessibility with overexpression of α-2,6 sialyltransferase produced IgG with significant levels of both α-2,6 and α-2,3 sialylation...
December 12, 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/27942918/immunological-low-dose-radiation-modulates-the-pediatric-medulloblastoma-antigens-and-enhances-antibody-dependent-cellular-cytotoxicity
#14
Arabinda Das, Daniel McDonald, Stephen Lowe, Amy-Lee Bredlau, Kenneth Vanek, Sunil J Patel, Samuel Cheshier, Ramin Eskandari
BACKGROUND: Immunotherapy can be an effective treatment for pediatric medulloblastoma (MB) patients. However, major subpopulations do not respond to immunotherapy, due to the lack of antigenic mutations or the immune-evasive properties of MB cells. Clinical observations suggest that radiation therapy (RT) may expand the therapeutic reach of immunotherapy. The aim of the present investigation is to study the effect of low-dose X-ray radiation (LDXR, 1 Gy) on the functional immunological responses of MB cells (DAOY, D283, and D341)...
December 9, 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/27942585/tissue-memory-b-cell-repertoire-analysis-after-alvac-aidsvax-b-e-gp120-immunization-of-rhesus-macaques
#15
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/27938486/a-comparison-of-exogenous-labels-for-the-histological-identification-of-transplanted-neural-stem-cells
#16
Francesca Nicholls, Jessie Liu, Michel Modo
The interpretation of cell transplantation experiments is often dependent on the presence of an exogenous label for theidentification of implanted cells. The exogenous labels Hoechst 33342, 5-Bromo-2’-deoxyuridine (BrdU), PKH26, and Qtracker were compared for their labeling efficiency, cellular effects and reliability to identify a human neural stem cell (hNSC) line implanted intracerebrally into the rat brain. Hoechst 33342 (2 mg/mL) exhibited a delayed cytotoxicity that killed all cells within 7 days...
3, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27914742/influenza-virus-specific-antibody-dependent-cellular-cytoxicity-induced-by-vaccination-or-natural-infection
#17
Rory D de Vries, Nella J Nieuwkoop, Mark Pronk, Erwin de Bruin, Geert Leroux-Roels, Elisabeth G W Huijskens, Rob S van Binnendijk, Florian Krammer, Marion P G Koopmans, Guus F Rimmelzwaan
Influenza viruses are responsible for substantial morbidity and mortality during seasonal epidemics. Vaccination is the most effective method to prevent infection, however due to antigenic drift of the viral surface protein hemagglutinin (HA), annual influenza virus vaccination is required. In addition to seasonal viruses, certain (avian) influenza A viruses of other subtypes, like H5N1 or H7N9, cause sporadic zoonotic infections. Therefore, the availability of game-changing novel vaccines that induce "universal" immune responses to a wide variety of influenza A virus subtypes is highly desirable...
January 5, 2017: Vaccine
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#18
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27906678/humoral-immune-responses-toward-tumor-derived-antigens-in-previously-untreated-patients-with-chronic-lymphocytic-leukemia
#19
Valentina Griggio, Giorgia Mandili, Candida Vitale, Michela Capello, Paolo Macor, Sara Serra, Barbara Castella, Silvia Peola, Myriam Foglietta, Daniela Drandi, Paola Omedé, Daniele Sblattero, Paola Cappello, Roberto Chiarle, Silvia Deaglio, Mario Boccadoro, Francesco Novelli, Massimo Massaia, Marta Coscia
In chronic lymphocytic leukemia (CLL) the occurrence and the impact of antibody responses toward tumor-derived antigens are largely unexplored. Our serological proteomic data show that antibodies toward 47 identified antigens are detectable in 29 out of 35 patients (83%) with untreated CLL. The glycolytic enzyme alpha-enolase (ENO1) is the most frequently recognized antigen (i.e. 54% of CLL sera). We show that ENO1 is upregulated in the proliferating B-cell fraction of CLL lymph nodes. In CLL cells of the peripheral blood, ENO1 is exclusively expressed at the intracellular level, whereas it is exposed on the surface of apoptotic leukemic cells...
November 30, 2016: Oncotarget
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
#20
Zhiwei Hu, Jie Xu, Jijun Cheng, Elizabeth McMichael, Lianbo Yu, William E Carson
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...
26, 2016: Oncotarget
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