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Antibody dependent cellular cytotoxicity

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https://www.readbyqxmd.com/read/29041009/fcgr2a-and-fcgr3a-genotypes-correlate-with-farletuzumab-response-in-patients-with-first-relapsed-ovarian-cancer-exhibiting-low-ca125
#1
Wenquan Wang, Elizabeth B Somers, Erin N Ross, J Bradford Kline, Daniel J O'Shannessy, Charles Schweizer, Susan Weil, Luigi Grasso, Nicholas C Nicolaides
Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha and elicits an anti-tumor response via immune effector activity. Recent studies from a global phase 3 trial in ovarian cancer patients treated with carboplatin/taxane plus farletuzumab found that the tumor-produced CA125 protein can suppress farletuzumab function via perturbing its engagement to the activating Fc-γ receptors CD32a (FCGR2A) and CD16a (FCGR3A). Previous reports have indicated that naturally occurring polymorphisms in both of these receptors may play a role in their ability to engage therapeutic antibodies and elicit an optimal immune response via antibody-dependent cellular cytotoxicity (ADCC)...
October 18, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/29028806/a-novel-immunotoxin-reveals-a-new-role-for-cd321-in-endothelial-cells
#2
Takeshi Fukuhara, Jia Kim, Shintaro Hokaiwado, Makiko Nawa, Hayato Okamoto, Tomohiko Kogiso, Tetsuro Watabe, Nobutaka Hattori
There are currently several antibody therapies that directly target tumors, and antibody-drug conjugates represent a novel moiety as next generation therapeutics. Here, we used a unique screening probe, DT3C, to identify functional antibodies that recognized surface molecules and functional epitopes, and which provided toxin delivery capability. Accordingly, we generated the 90G4 antibody, which induced DT3C-dependent cytotoxicity in endothelial cells. Molecular analysis revealed that 90G4 recognized CD321, a protein localized at tight junctions...
2017: PloS One
https://www.readbyqxmd.com/read/29021394/hiv-1-gp120-protein-and-mvagp140-boost-immunogens-increase-immunogenicity-of-a-dna-mva-hiv-1-vaccine
#3
Xiaoying Shen, Rahul Basu, Sheetal Sawant, David Beaumont, Sue Fen Kwa, Celia LaBranche, Kelly E Seaton, Nicole L Yates, David C Montefiori, Guido Ferrari, Linda S Wyatt, Bernard Moss, S Munir Alam, Barton F Haynes, Georgia D Tomaras, Harriet L Robinson
An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia Ankara (MVA) expressing HIV-1 Env on virus like particles. Here we evaluated whether the addition of a gp120 protein in alum or MVA expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime - MVA boost vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8 followed by three MVA boosts (with or without additional protein or MVAgp140) at weeks 18, 26 and 40...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29018953/frequency-and-proliferative-response-of-circulating-invariant-natural-killer-t-cells-in-pediatric-patients-with-malignant-solid-tumors
#4
Tomoro Hishiki, Naoko Mise, Kazuaki Harada, Fumie Ihara, Mariko Takami, Takeshi Saito, Keita Terui, Mitsuyuki Nakata, Shugo Komatsu, Hideo Yoshida, Shinichiro Motohashi
BACKGROUND: Invariant natural killer T (iNKT) cells play an important role in tumor immunity, enhancing both innate and acquired immunity. We have previously shown the enhancement of antibody-dependent cellular cytotoxicity against neuroblastoma by activated iNKT cells. As a first step towards clinical application, we studied the frequency and proliferative response of circulating iNKT cells in children with and without cancer. METHODS: Blood samples were collected from 10 patients with pediatric malignant solid tumors and 11 patients with non-neoplastic diseases (control)...
October 10, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28992681/ofatumumab-monoclonal-antibody-affinity-maturation-through-in-silico-modeling
#5
Zahra Payandeh, Masoumeh Rajabibazl, Yousef Mortazavi, Azam Rahim-Pour, Amir Hossein Taromchi
Background: Ofatumumab, an anti-CD20 mAb, was approved in 2009 for the treatment of chronic lymphocytic leukemia. This mAb acts through immune-mediated mechanisms, in particular complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by natural killer cells as well as antibody-dependent phagocytosis by macrophages. Apoptosis induction is another mechanism of this antibody. Computational docking is the method of predicting the conformation of an antibody-antigen from its separated elements...
October 10, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28982863/effects-of-adam10-and-adam17-inhibitors-on-natural-killer-cell-expansion-and-antibody-dependent-cellular-cytotoxicity-against-breast-cancer-cells-in-vitro
#6
Dang-Huan Pham, Ju-Sun Kim, Sang-Ki Kim, Dong-Jun Shin, Nguyen-Thanh-Tung Uong, Hoon Hyun, Mee Sun Yoon, Sin Jae Kang, Young Jae Ryu, Jin Seong Cho, Jung Han Yoon, Ji Shin Lee, Duck Cho, Soo-Hyeon Lee, Min Ho Park
BACKGROUND/AIM: The inhibition of a disintegrin and metalloproteinase (ADAM) has the potential to become a novel approach for natural killer (NK) cell-based cancer immunotherapy. Thus, the aim of this study was to investigate the influence of ADAM10 and ADAM17 inhibitors on expanded NK cell to enhance antibody-dependent cellular cytotoxicity (ADCC) in breast cancer cell lines. MATERIALS AND METHODS: NK cells were expanded in medium supplemented with an ADAM10 or ADAM17 inhibitor to prevent the shedding of soluble CD16/FcγRIII...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28982260/immunization-with-clinical-hiv-1-env-proteins-induces-broad-antibody-dependent-cellular-cytotoxicity-adcc-mediating-antibodies-in-a-rabbit-vaccination-model
#7
Ingrid Karlsson, Marie Borggren, Sanne Skov Jensen, Leo Heyndrickx, Guillaume Stewart-Jones, Gabriella Scarlatti, Anders Fomsgaard
The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, e.g., antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone and DNA prime with protein boost...
October 6, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28978939/non-neutralizing-antibodies-targeting-the-v1v2-domain-of-hiv-exhibit-strong-antibody-dependent-cell-mediated-cytotoxic-activity
#8
Luzia M Mayr, Thomas Decoville, Sylvie Schmidt, Géraldine Laumond, Jéromine Klingler, Camille Ducloy, Seiamak Bahram, Susan Zolla-Pazner, Christiane Moog
The development of an effective vaccine against HIV-1 has proven to be challenging. Broadly neutralizing antibodies (bNAbs), whilst exhibiting neutralization breadth and potency, are elicited only in a small subset of infected individuals and have yet to be induced by vaccination. Case-control studies of RV144 identified an inverse correlation of HIV-1 infection risk with antibodies (Abs) to the V1V2 region of gp120 with high antibody-dependent cellular cytotoxicity (ADCC) activity. The neutralizing activity of Abs was not found to contribute to this protective outcome...
October 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28978026/enhanced-antiproliferative-activity-of-antibody-functionalized-polymeric-nanoparticles-for-targeted-delivery-of-anti-mir-21-to-her2-positive-gastric-cancer
#9
Feng-Lei Wu, Jian Zhang, Wei Li, Bao-Xiang Bian, Yi-Dong Hong, Zi-Yan Song, Hui-Yu Wang, Fang-Bo Cui, Ru-Tian Li, Qin Liu, Xiao-Dong Jiang, Xiao-Min Li, Jun-Nian Zheng
MiR-21 is an oncogenic miR frequently elevated in gastric cancer. Overexpression of miR-21 decreases the sensitivity of gastric cancer cells to trastuzumab, which is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2. However, optimization of miRNA or its anti-miRNA oligonucleotides (AMOs) for delivery is a challenge. Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including AMOs. This study is a continuation of our earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target gastric cancer cells with HER2 receptor over-expression using anti-miRNA-21 antisense oligonucleotides (AMO-21)...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28970093/a-mathematical-model-of-antibody-dependent-cellular-cytotoxicity-adcc
#10
F Hoffman, D Gavaghan, J Osborne, I P Barrett, T You, H Ghadially, R Sainson, R W Wilkinson, H M Byrne
Immunotherapies exploit the immune system to target and kill cancer cells, while sparing healthy tissue. Antibody therapies, an important class of immunotherapies, involve the binding to specific antigens on the surface of the tumour cells of antibodies that activate natural killer (NK) cells to kill the tumour cells. Preclinical assessment of molecules that may cause antibody-dependent cellular cytotoxicity (ADCC) involves co-culturing cancer cells, NK cells and antibody in vitro for several hours and measuring subsequent levels of tumour cell lysis...
September 29, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28969431/intradermal-hiv-1-dna-immunization-using-needle-free-zetajet-sup-tm-sup-injection-followed-by-hiv-modified-vaccinia-virus-ankara-vaccination-is-safe-and-immunogenic-in-mozambican-young-adults-a-phase-i-randomized-controlled-trial
#11
Edna Omar Viegas, Nelson Tembe, Charlotta Nilsson, Bindiya Meggi, Cremildo Maueia, Orvalho Augusto, Richard Stout, Gabriella Scarlatti, Guido Ferrari, Patricia Earl, Britta Wahren, Sören Andersson, Merlin Robb, Nafissa Osman, Gunnel Biberfeld, Ilesh Jani, Eric Sandström
We assessed safety and immunogenicity of HIV-DNA priming using Zetajet<sup>TM</sup>, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 µg (n = 10; 2 x 0.1mL) or 1200 µg (n = 10; 2 x 0.2mL) of HIV-DNA (3 mg/mL), followed by two boosts of 10<sup>8</sup>pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups...
October 2, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28968759/safety-and-immunogenicity-of-pennvax%C3%A2-g-dna-prime-administered-by-biojector%C3%A2-2000-or-cellectra%C3%A2-electroporation-device-with-modified-vaccinia-ankara-cmdr-boost
#12
Julie A Ake, Alexandra Schuetz, Poonam Pegu, Lindsay Wieczorek, Michael A Eller, Hannah Kibuuka, Fredrick Sawe, Leonard Maboko, Victoria Polonis, Nicos Karasavva, David Weiner, Arthur Sekiziyivu, Josphat Kosgei, Marco Missanga, Arne Kroidl, Philipp Mann, Silvia Ratto-Kim, Leigh Anne Eller, Patricia Earl, Bernard Moss, Julie Dorsey-Spitz, Mark Milazzo, G Laissa Ouedraogo, Farrukh Rizvi, Jian Yan, Amir S Khan, Sheila Peel, Niranjan Y Sardesai, Nelson L Michael, Viseth Ngauy, Mary Marovich, Merlin L Robb
Background: We report the first-in-human safety and immunogenicity evaluation of PENNVAX®-G DNA/ MVA-CMDR prime-boost HIV vaccine, with intramuscular DNA delivery by either Biojector® 2000 needle free injection system (Biojector) or by CELLECTRA® electroporation device. Methods: Healthy, HIV-uninfected adults were randomized to receive 4 mg PENNVAX®-G DNA delivered IM by Biojector or electroporation at baseline and week 4 followed by IM injection of 108 pfu MVA-CMDR at week 12 and 24...
September 2, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28959256/functionally-active-fc-mutant-antibodies-recognizing-cancer-antigens-generated-rapidly-at-high-yields
#13
Kristina M Ilieva, Judit Fazekas-Singer, Daniela Y Achkova, Tihomir S Dodev, Silvia Mele, Silvia Crescioli, Heather J Bax, Anthony Cheung, Panagiotis Karagiannis, Isabel Correa, Mariangela Figini, Rebecca Marlow, Debra H Josephs, Andrew J Beavil, John Maher, James F Spicer, Erika Jensen-Jarolim, Andrew N Tutt, Sophia N Karagiannis
Monoclonal antibodies find broad application as therapy for various types of cancer by employing multiple mechanisms of action against tumors. Manipulating the Fc-mediated functions of antibodies that engage immune effector cells, such as NK cells, represents a strategy to influence effector cell activation and to enhance antibody potency and potentially efficacy. We developed a novel approach to generate and ascertain the functional attributes of Fc mutant monoclonal antibodies. This entailed coupling single expression vector (pVitro1) antibody cloning, using polymerase incomplete primer extension (PIPE) polymerase chain reaction, together with simultaneous Fc region point mutagenesis and high yield transient expression in human mammalian cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28955328/co-delivery-of-dual-toll-like-receptor-agonists-and-antigen-in-poly-lactic-co-glycolic-acid-polyethylenimine-cationic-hybrid-nanoparticles-promote-efficient-in-vivo-immune-responses
#14
Mahboubeh Ebrahimian, Maryam Hashemi, Mohsen Maleki, Gholamreza Hashemitabar, Khalil Abnous, Mohammad Ramezani, Alireza Haghparast
Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28952147/genetic-variation-of-human-neutrophil-fc%C3%AE-receptors-and-sirp%C3%AE-in-antibody-dependent-cellular-cytotoxicity-towards-cancer-cells
#15
Louise W Treffers, Xi Wen Zhao, Joris van der Heijden, Sietse Q Nagelkerke, Dieke J van Rees, Patricia Gonzalez, Judy Geissler, Paul Verkuijlen, Michel van Houdt, Martin de Boer, Taco W Kuijpers, Timo K van den Berg, Hanke L Matlung
The efficacy of cancer therapeutic antibodies varies considerably among patients. Anti-cancer antibodies act through different mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) triggered via Fcγ receptors (FcγR). This phagocyte ADCC can be promoted by interference with CD47-SIRPα interactions, but the magnitude of this enhancement also varies among individuals. Both FcγR and SIRPα display considerable genetic variation, and we investigated whether this explains some of the variability in ADCC...
September 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28945315/quantitating-adcc-against-adherent-cells-impedance-based-detection-is-superior-to-release-membrane-permeability-or-caspase-activation-assays-in-resolving-antibody-dose-response
#16
Gábor Tóth, János Szöllősi, György Vereb
Monoclonal antibody-based immunotherapeutics will dominate Pharma's next generation of blockbuster drugs, and Fc-associated functions, including antibody dependent cellular cytotoxicity (ADCC) are among the highly desired activities mediated by these antibodies. Therefore, quantitative evaluation of ADCC is required during drug development. Our objective was to find the most suitable and reliable nonradioactive method for quantitative analysis of in vitro ADCC against adherent cells, which often serve as models for solid tumors...
September 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28941150/brentuximab-vedotin-exerts-profound-antiproliferative-and-pro-apoptotic-efficacy-in-cd30-positive-as-well-as-cocultured-cd30-negative-germ-cell-tumour-cell-lines
#17
Stefan Schönberger, Cornelius van Beekum, Barbara Götz, Daniel Nettersheim, Hubert Schorle, Dominik T Schneider, Anna Casati, Rogerio B Craveiro, Gabriele Calaminus, Dagmar Dilloo
Prognosis in patients suffering from high-risk, refractory and relapsed germ cell tumours (GCT) often comprising of CD30-positive embryonal carcinoma (EC) components remains poor. Thus, novel treatment strategies are warranted. The antibody-drug conjugate (ADC) brentuximab vedotin delivers the potent antimitotic drug monomethyl auristatin E (MMAE) to CD30-expressing tumour cells. After CD30 binding, internalization and intracellular linker cleavage cytotoxic MMAE can efflux and eradicate neighbouring CD30-negative cells...
September 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28935106/chemoenzymatic-glycan-remodeling-of-natural-and-recombinant-glycoproteins
#18
Qiang Yang, Lai-Xi Wang
N-glycosylation plays important roles in modulating the biological functions of glycoproteins, such as protein folding, stability, and immunogenicity. However, acquiring homogeneous glycoforms of glycoproteins has been a challenging task for functional studies and therapeutic applications. In this chapter, we describe an efficient chemoenzymatic glycan remodeling protocol for making homogeneous glycoproteins that involves enzymatic deglycosylation and subsequent reglycosylation procedures. Two therapeutic glycoproteins, Herceptin (trastuzumab, a therapeutic monoclonal antibody) and erythropoietin (EPO, a glycoprotein hormone), were chosen as the model systems...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#19
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928215/influenza-virus-hemagglutinin-stalk-specific-antibodies-in-human-serum-are-a-surrogate-marker-for-in-vivo-protection-in-a-serum-transfer-mouse-challenge-model
#20
Henning Jacobsen, Madhusudan Rajendran, Angela Choi, Haakon Sjursen, Karl A Brokstad, Rebecca J Cox, Peter Palese, Florian Krammer, Raffael Nachbagauer
The immunogenicity of current influenza virus vaccines is assessed by measuring an increase of influenza virus-specific antibodies in a hemagglutination inhibition assay. This method exclusively measures antibodies against the hemagglutinin head domain. While this domain is immunodominant, it has been shown that hemagglutination inhibition titers do not always accurately predict protection from disease. In addition, several novel influenza virus vaccines that are currently under development do not target the hemagglutinin head domain, but rather more conserved sites, including the hemagglutinin stalk...
September 19, 2017: MBio
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