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Increasing ADCC

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https://www.readbyqxmd.com/read/29273355/what-is-the-most-important-for-elite-control-genetic-background-of-patient-genetic-background-of-partner-both-or-neither-description-of-complete-natural-history-within-a-couple-of-msm
#1
M Bendenoun, A Samri, V Avettand-Fènoël, S Cardinaud, B Descours, G Carcelain, M-C Mazeron, J-F Bergmann, A Urrutia, A Moris, C Rouzioux, F Simon, P Andre, M Pocard, X Dray, T Mourez, V Vieillard, B Autran, F Barin, P Sellier
BACKGROUND: We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background. METHODS: HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined. FINDINGS: Two HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay...
December 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29247515/intrahepatic-and-peripheral-blood-phenotypes-of-nk-and-t-cells-differential-surface-expression-of-kir-receptors
#2
Ariel Podhorzer, Andrés Machicote, Santiago Belen, Leandro Lauferman, Oscar Imventarza, Silvina Montal, Sebastián Marciano, Omar Galdame, Luis G Podesta, Leonardo Fainboim
Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood NK, NKT and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activatory marker NKp44...
December 16, 2017: Immunology
https://www.readbyqxmd.com/read/29245952/the-humanized-anti-human-amhrii-mab-3c23k-exerts-an-anti-tumor-activity-against-human-ovarian-cancer-through-tumor-associated-macrophages
#3
Houcine Bougherara, Fariba Némati, André Nicolas, Gérald Massonnet, Martine Pugnière, Charlotte Ngô, Marie-Aude Le Frère-Belda, Alexandra Leary, Jérôme Alexandre, Didier Meseure, Jean-Marc Barret, Isabelle Navarro-Teulon, André Pèlegrin, Sergio Roman-Roman, Jean-François Prost, Emmanuel Donnadieu, Didier Decaudin
Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, such as human ovarian cancers (OCs). On this basis, a humanized glyco-engineered monoclonal antibody (3C23K) has been developed. The aim of this study was therefore to experimentally confirm the therapeutic potential of 3C23K in human OCs. We first determined by immunofluorescence, immunohistochemistry and cytofluorometry analyses the expression of AMHRII in patient's tumors and found that a majority (60 to 80% depending on the detection technique) of OCs were positive for this marker...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222435/long-term-maintenance-of-peripheral-blood-derived-human-nk-cells-in-a-novel-human-il-15-transgenic-nog-mouse
#4
Ikumi Katano, Chiyoko Nishime, Ryoji Ito, Tsutomu Kamisako, Takuma Mizusawa, Yuyo Ka, Tomoyuki Ogura, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
We generated a novel mouse strain expressing transgenic human interleukin-15 (IL-15) using the severe immunodeficient NOD/Shi-scid-IL-2Rγ null (NOG) mouse genetic background (NOG-IL-15 Tg). Human natural killer (NK) cells, purified from the peripheral blood (hu-PB-NK) of normal healthy donors, proliferated when transferred into NOG-IL-15 Tg mice. In addition, the cell number increased, and the hu-PB-NK cells persisted for 3 months without signs of xenogeneic graft versus host diseases (xGVHD). These in vivo-expanded hu-PB-NK cells maintained the original expression patterns of various surface antigens, including NK receptors and killer cell immunoglobulin-like receptor (KIR) molecules...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29209569/resistance-to-her2-targeted-anti-cancer-drugs-is-associated-with-immune-evasion-in-cancer-cells-and-their-derived-extracellular-vesicles
#5
Vanesa G Martinez, Sadhbh O'Neill, Josephine Salimu, Susan Breslin, Aled Clayton, John Crown, Lorraine O'Driscoll
Neuromedin U (NmU) -a neuropeptide belonging to the neuromedin family- plays a substantial role in HER2-positive breast cancer, correlating with increased aggressiveness, resistance to HER2-targeted therapies and overall significantly poorer outcome for patients. However, the mechanism through which it exerts these effects remains unclear. To elucidate this, initially we used HER2-positive breast cancer cells stably over-expressing NmU. These cells and their released extracellular vesicles (EVs) had increased amounts of the immunosuppressive cytokine TGFβ1 and the lymphocyte activation inhibitor PD-L1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29194123/anti-hiv-1-antibody-dependent-cellular-cytotoxicity-is-there-more-to-antibodies-than-neutralization
#6
Wen Shi Lee, Stephen J Kent
PURPOSE OF REVIEW: An increasing body of evidence suggests that nonneutralizing Fc effector functions including antibody-dependent cellular cytotoxicity (ADCC) contribute to protection against HIV-1 acquisition. We discuss recent advances in anti-HIV-1 ADCC research with a particular focus on ADCC mediated by Env-specific antibodies in vitro and in vivo, the curative potential of HIV-1-specific ADCC antibodies and the mechanisms of HIV-1 resistance to ADCC. RECENT FINDINGS: ADCC activities of broadly neutralizing and nonneutralizing monoclonal antibody panels were recently characterized in vitro against several lab-adapted and primary isolates of HIV-1...
November 30, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29174687/membrane-anchored-stalk-domain-of-influenza-ha-enhanced-immune-responses-in-mice
#7
Dandan Gao, Yan Chen, Dong Han, Qiulan Qi, Xianliang Sun, Han Zhang, Hao Feng, Min Wang
Current strategies for influenza virus vaccines primarily aim to elicit immune responses towards the globular head domain of the hemagglutinin (HA) protein so that binding of the virus to membrane receptors on the host cells is inhibited. In the present study, we show a novel strategy to generate immunity against the highly conserved region of the influenza virus. The globular head domain was replaced by different linkers to generate a headless HA (stalk domain) and then coexpressed with influenza M1 proteinin Tni insect cells...
November 21, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29173063/development-of-a-pre-glycoengineered-cho-k1-host-cell-line-for-the-expression-of-antibodies-with-enhanced-fc-mediated-effector-function
#8
Oliver Popp, Samuel Moser, Jörg Zielonka, Petra Rüger, Silke Hansen, Oliver Plöttner
Novel biotherapeutic glycoproteins, like recombinant monoclonal antibodies (mAbs) are widely used for the treatment of numerous diseases. The N-glycans attached to the constant region of an antibody have been demonstrated to be crucial for the biological efficacy. Even minor modifications of the N-glycan structure can dictate the potency of IgG effector functions such as the antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Here, we present the development of a glycoengineered CHO-K1 host cell line (HCL), stably expressing β1,4-N-Acetylglucoseaminyltransferase III (GnT-III) and α-mannosidase II (Man-II), for the expression of a-fucosylated antibodies with enhanced Fc-mediated effector function...
November 27, 2017: MAbs
https://www.readbyqxmd.com/read/29150961/modulation-of-igg1-immunoeffector-function-by-glycoengineering-of-the-gdp-fucose-biosynthesis-pathway
#9
Ronan M Kelly, Ronald L Kowle, Zhirui Lian, Beth A Strifler, Derrick R Witcher, Bhavin S Parekh, Tongtong Wang, Christopher C Frye
Cross-linking of the Fcγ receptors expressed on the surface of hematopoietic cells by IgG immune complexes triggers the activation of key immune effector mechanisms, including antibody-dependent cell mediated cytotoxicity (ADCC). A conserved N-glycan positioned at the N-terminal region of the IgG CH 2 domain is critical in maintaining the quaternary structure of the molecule for Fcγ receptor engagement. The removal of a single core fucose residue from the N-glycan results in a considerable increase in affinity for FcγRIIIa leading to an enhanced receptor-mediated immunoeffector function...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29123953/pd-1-blockade-augments-anti-neuroblastoma-immune-response-induced-by-anti-gd2-antibody-ch14-18-cho
#10
Nikolai Siebert, Maxi Zumpe, Madlen Jüttner, Sascha Troschke-Meurer, Holger N Lode
Immunotherapy with anti-GD2 antibody (Ab) ch14.18/CHO is effective for treatment of high-risk neuroblastoma (NB) patients and is mainly based on GD2-specific Ab-dependent cellular cytotoxicity (ADCC). Strategies to further enhance the efficacy are important and currently explored in prospective clinical trials randomizing ch14.18/CHO ± IL-2. Recently, expression of programmed death 1 (PD-1) inhibitory receptor by effector cells and its ligand (PD-L1) by tumor cells has been shown. Here, we report for the first time effects of PD-1 blockade on ch14...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29101107/cytokines-in-cancer-immunotherapy
#11
Thomas A Waldmann
Cytokines that control the immune response were shown to have efficacy in preclinical murine cancer models. Interferon (IFN)-α is approved for treatment of hairy cell leukemia, and interleukin (IL)-2 for the treatment of advanced melanoma and metastatic renal cancer. In addition, IL-12, IL-15, IL-21, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been evaluated in clinical trials. However, the cytokines as monotherapy have not fulfilled their early promise because cytokines administered parenterally do not achieve sufficient concentrations in the tumor, are often associated with severe toxicities, and induce humoral or cellular checkpoints...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29062024/conformational-effects-of-n-glycan-core-fucosylation-of-immunoglobulin-g-fc-region-on-its-interaction-with-fc%C3%AE-receptor-iiia
#12
Yoshitake Sakae, Tadashi Satoh, Hirokazu Yagi, Saeko Yanaka, Takumi Yamaguchi, Yuya Isoda, Shigeru Iida, Yuko Okamoto, Koichi Kato
Antibody-dependent cellular cytotoxicity (ADCC) is promoted through interaction between the Fc region of immunoglobulin G1 (IgG1) and Fcγ receptor IIIa (FcγRIIIa), depending on N-glycosylation of these glycoproteins. In particular, core fucosylation of IgG1-Fc N-glycans negatively affects this interaction and thereby compromises ADCC activity. To address the mechanisms of this effect, we performed replica-exchange molecular dynamics simulations based on crystallographic analysis of a soluble form of FcγRIIIa (sFcγRIIIa) in complex with IgG1-Fc...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021394/hiv-1-gp120-protein-and-mvagp140-boost-immunogens-increase-immunogenicity-of-a-dna-mva-hiv-1-vaccine
#13
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/29019081/modification-of-nk-cell-subset-repartition-and-functions-in-granulocyte-colony-stimulating-factor-mobilized-leukapheresis-after-expansion-with-il-15
#14
Yu Xiong, Manon Mouginot, Loic Reppel, Chongsheng Qian, Jean-Francois Stoltz, Danièle Bensoussan, Véronique Decot
The ability of natural killer (NK) cells to kill tumor cells without antigen recognition makes them appealing as an adoptive immunotherapy. However, NK cells are not routinely used in the context of leukemic relapse after hematopoietic stem cell transplantation. Patients who experience relapse can be treated with donor lymphocyte infusions (DLI) based on small-cell fractions frozen at the time of transplantation. Since peripheral blood stem cells (PBSCs) are increasingly used as a stem cell source and as a source of cells for DLI, we aimed to evaluate the impact of G-SCF mobilization on NK cell phenotype, subset repartition, and functionality...
December 2017: Immunologic Research
https://www.readbyqxmd.com/read/28989534/activation-of-janus-kinase-1-confers-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#15
Dan Liu, Yi Huang, Li Zhang, Dong-Ni Liang, Li Li
The activation of Janus kinase 1 (JAK1) has been reported to occur in non-small cell lung cancer (NSCLC), activating the JAK/signal transducers and activators of transcription cascade. However, the association between JAK1 activation and the prognostic value in NSCLC remains unclear. The present study initially investigated the association between expression of the activated form of JAK1 (p-JAK1) and prognosis in patients with NSCLC. A cohort of 142 resected primary NSCLC tissue samples, including 74 adenocarcinoma (ADCC) and 68 squamous cell carcinoma samples, were analyzed...
October 2017: Oncology Letters
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
#16
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/28945315/quantitating-adcc-against-adherent-cells-impedance-based-detection-is-superior-to-release-membrane-permeability-or-caspase-activation-assays-in-resolving-antibody-dose-response
#17
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/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#18
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
#19
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
https://www.readbyqxmd.com/read/28811973/nk-cell-dysfunction-in-chronic-lymphocytic-leukemia-is-associated-with-loss-of-the-mature-cells-expressing-inhibitory-killer-cell-ig-like-receptors
#20
Alexander W MacFarlane, Mowafaq Jillab, Mitchell R Smith, R Katherine Alpaugh, Marion E Cole, Samuel Litwin, Michael M Millenson, Tahseen Al-Saleem, Adam D Cohen, Kerry S Campbell
A prospective analysis of natural killer (NK) cell phenotype and function was performed on fresh peripheral blood samples from untreated patients with B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Compared to healthy controls, CD56(dim) NK cells in CLL patients displayed reduced expression of the NKG2D activating receptor and increased CD27 expression, which indicates declines in mature cells. In addition, NK cells from CLL patients showed reduced degranulation responses toward transformed B cells alone or with rituximab and were more sensitive to activation-induced cell death...
2017: Oncoimmunology
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