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24 results on '"Rharbaoui, Faiza"'

1. Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study

Author

Kelly, Kevin R, Ailawadhi, Sikander, Siegel, David S, Heffner, Leonard T, Somlo, George, Jagannath, Sundar, Zimmerman, Todd M, Munshi, Nikhil C, Madan, Sumit, Chanan-Khan, Asher, Lonial, Sagar, Chandwani, Suraj, Minasyan, Ashot, Ruehle, Markus, Barmaki-Rad, Farima, Abdolzade-Bavil, Afsaneh, Rharbaoui, Faiza, Herrmann-Keiner, Eva, Haeder, Thomas, Wartenberg-Demand, Andrea, and Anderson, Kenneth C

Published
2021
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3. Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist

Author

Bossart, Martin, Wagner, Michael, Elvert, Ralf, Evers, Andreas, Hubschle, Thomas, Kloeckener, Tim, Lorenz, Katrin, Moessinger, Christine, Eriksson, Olof, Velikyan, Irina, Pierrou, Stefan, Johansson, Lars, Dietert, Gabriele, Dietz-Baum, Yasmin, Kissner, Thomas, Nowotny, Irene, Einig, Christine, Jan, Christelle, Rharbaoui, Faiza, Gassenhuber, Johann, Prochnow, Hans-Peter, Agueusop, Inoncent, Porksen, Niels, Smith, William B., Nitsche, Almut, Konkar, Anish, Bossart, Martin, Wagner, Michael, Elvert, Ralf, Evers, Andreas, Hubschle, Thomas, Kloeckener, Tim, Lorenz, Katrin, Moessinger, Christine, Eriksson, Olof, Velikyan, Irina, Pierrou, Stefan, Johansson, Lars, Dietert, Gabriele, Dietz-Baum, Yasmin, Kissner, Thomas, Nowotny, Irene, Einig, Christine, Jan, Christelle, Rharbaoui, Faiza, Gassenhuber, Johann, Prochnow, Hans-Peter, Agueusop, Inoncent, Porksen, Niels, Smith, William B., Nitsche, Almut, and Konkar, Anish

Abstract

Unimolecular triple incretins, combining the activity of glucagon-like peptide-1 (GLP-1), glucose -dependent insulinotropic polypeptide (GIP), and glucagon (GCG), have demonstrated reduction in body weight and improved glucose control in rodent models. We developed SAR441255, a synthetic peptide agonist of the GLP-1, GCG, and GIP receptors, structurally based on the exendin-4 sequence. SAR441255 displays high potency with balanced activation of all three target receptors. In animal models, metabolic outcomes were superior to results with a dual GLP-1/GCG receptor agonist. Preclinical in vivo positron emission tomography imaging demonstrated SAR441255 binding to GLP-1 and GCG receptors. In healthy subjects, SAR441255 improved glycemic control during a mixed-meal tolerance test and impacted biomarkers for GCG and GIP receptor activation. Single doses of SAR441255 were well tolerated. The results demonstrate that integrating GIP activity into dual GLP-1 and GCG receptor agonism provides improved effects on weight loss and glycemic control while buffering the diabetogenic risk of chronic GCG receptor agonism.

Published
2022
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4. Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist

Author

Bossart, Martin, primary, Wagner, Michael, additional, Elvert, Ralf, additional, Evers, Andreas, additional, Hübschle, Thomas, additional, Kloeckener, Tim, additional, Lorenz, Katrin, additional, Moessinger, Christine, additional, Eriksson, Olof, additional, Velikyan, Irina, additional, Pierrou, Stefan, additional, Johansson, Lars, additional, Dietert, Gabriele, additional, Dietz-Baum, Yasmin, additional, Kissner, Thomas, additional, Nowotny, Irene, additional, Einig, Christine, additional, Jan, Christelle, additional, Rharbaoui, Faiza, additional, Gassenhuber, Johann, additional, Prochnow, Hans-Peter, additional, Agueusop, Inoncent, additional, Porksen, Niels, additional, Smith, William B., additional, Nitsche, Almut, additional, and Konkar, Anish, additional

Published
2022
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7. Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial

Author

van Vollenhoven, Ronald F, primary, Keystone, Edward Clark, additional, Strand, Vibeke, additional, Pacheco-Tena, Cesar, additional, Vencovský, Jiří, additional, Behrens, Frank, additional, Racewicz, Arthur, additional, Zipp, Daniela, additional, Rharbaoui, Faiza, additional, Wolter, Ralf, additional, Knierim, Luise, additional, Schmeidl, Rainer, additional, Zhou, Xuefei, additional, Aigner, Silke, additional, Dälken, Benjamin, additional, and Wartenberg-Demand, Andrea, additional

Published
2018
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8. A phase 2b study evaluating the efficacy and safety of subcutaneously administered tregalizumab in subjects with active Rheumatoid Arthritis (RA) despite treatment with Methotrexate (MTX)

Author

Vollenhoven, Ronald F., Keystone, Edward C., Strand, Vibeke, Pacheco-Tena, Cesar, Jiri Vencovsky, Behrens, Frank, Zipp, Daniela, Rharbaoui, Faiza, Wolter, Ralf, Tiemann, Rolf-Dietrich, Knierim, Luise, Schmeidl, Rainer, Zhou, Xuefei, Aigner, Silke, Daelken, Benjamin, Wartenberg-Demand, Andrea, and Publica

Abstract

Background/Purpose: In autoimmune diseases reduced numbers and functional impairment of regulatory T cells (Tregs) have been observed (1). Tregalizumab (BT-061) is a humanized, anti-CD4 mAb, inducing selective Treg activation in vitro. Previous trials suggested efficacy in RA at doses >25 mg subcutaneously (SC). In a population PK/PD analysis, down-modulation of CD4 expression was identified as a biomarker to monitor CD4 target engagement in humans. Methods: This two-part, Phase 2b randomized controlled trial (RCT) included subjects with active RA for >6 months despite MTX (>15mg/wk), with >6/28 TJC, >6/28 SJC and elevated CRP or ESR. Subjects were randomized to receive 25 mg, 100 mg, 200 mg, or PBO once-weekly SC injection + MTX over 24 wks. Primary endpoint was ACR20 at wk 12. At wk 12 (end of Main part I), non-responders were re-randomized to active treatment or higher doses. Subjects responding at wk 24 (end of Main part II) could extend treatment for an additional 24 wks. A data safety monitoring board (DSMB) was established for safety evaluation throughout the study. Results: Of 321 subjects enrolled from Europe, USA, Canada, Russia and Mexico, 37 (11.5%) withdrew at < wk 12. Demographics and baseline disease characteristics were well balanced across groups: mean SJC and TJC 16 and 24, respectively; CRP 11.7 mg/L, DAS (ESR) 6.58 and HAQ-DI 1.56. ACR20 responders at wk 12 (42.3%/47%/44.3% vs. 35.2% in 25 mg, 100 mg, 200 mg groups and PBO, respectively), ACR20 responders at wk 24 and secondary endpoints did not differ significantly between tregalizumab groups and PBO. However, dose dependent modulation of CD4 expression on T cells occurred rapidly with BT-061 treatment, as predicted from previous analyses. Through wk 12, TEAE (39.4% and 37.5%) and serious TEAEs rates (2.1% and 1.3%) were similar between BT-061 and PBO. For responder at wk 24, TEAEs (48.3% and 52.3%) were similar between BT-061 and PBO. Serious TEAEs were only reported in BT-061 treated subjects (2%). Three deaths occurred considered unrelated to treatment (car accident, acute coronary syndrome, death of unknown cause in a war area). There was no difference in infections between tregalizumab and PBO. One serious infection (peritonitis) occurred at wk 22 in the 25 mg dose group. Apart from acute coronary syndrome with fatal outcome, no further MACE events, Tuberculosis, opportunistic infections nor malignancies were reported. Conclusion: No tested doses of tregalizumab demonstrated significant efficacy improving signs and symptoms of active RA based on ACR20 responses at wk 12 and 24 despite dose dependent down-modulation of CD4 expression. Tregalizumab was generally well tolerated.

Published
2015

11. Erratum: Corrigendum: A selective inhibitor reveals PI3Kγ dependence of TH17 cell differentiation

Author

Bergamini, Giovanna, primary, Bell, Kathryn, additional, Shimamura, Satoko, additional, Werner, Thilo, additional, Cansfield, Andrew, additional, Müller, Katrin, additional, Perrin, Jessica, additional, Rau, Christina, additional, Ellard, Katie, additional, Hopf, Carsten, additional, Doce, Carola, additional, Leggate, Daniel, additional, Mangano, Raffaella, additional, Mathieson, Toby, additional, O'Mahony, Alison, additional, Plavec, Ivan, additional, Rharbaoui, Faiza, additional, Reinhard, Friedrich, additional, Savitski, Mikhail M, additional, Ramsden, Nigel, additional, Hirsch, Emilio, additional, Drewes, Gerard, additional, Rausch, Oliver, additional, Bantscheff, Marcus, additional, and Neubauer, Gitte, additional

Published
2012
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12. A selective inhibitor reveals PI3Kγ dependence of TH17 cell differentiation

Author

Bergamini, Giovanna, primary, Bell, Kathryn, additional, Shimamura, Satoko, additional, Werner, Thilo, additional, Cansfield, Andrew, additional, Müller, Katrin, additional, Perrin, Jessica, additional, Rau, Christina, additional, Ellard, Katie, additional, Hopf, Carsten, additional, Doce, Carola, additional, Leggate, Daniel, additional, Mangano, Raffaella, additional, Mathieson, Toby, additional, O'Mahony, Alison, additional, Plavec, Ivan, additional, Rharbaoui, Faiza, additional, Reinhard, Friedrich, additional, Savitski, Mikhail M, additional, Ramsden, Nigel, additional, Hirsch, Emilio, additional, Drewes, Gerard, additional, Rausch, Oliver, additional, Bantscheff, Marcus, additional, and Neubauer, Gitte, additional

Published
2012
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17. Efficient mucosal delivery of the HIV-1 Tat protein using the synthetic lipopeptide MALP-2 as adjuvant

Author

Borsutzky, Stefan, primary, Fiorelli, Valeria, additional, Ebensen, Thomas, additional, Tripiciano, Antonella, additional, Rharbaoui, Faiza, additional, Scoglio, Arianna, additional, Link, Claudia, additional, Nappi, Filomena, additional, Morr, Michael, additional, Buttó, Stefano, additional, Cafaro, Aurelio, additional, Mühlradt, Peter F., additional, Ensoli, Barbara, additional, and Guzmán, Carlos A., additional

Published
2003
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20. A selective inhibitor reveals PI3K? dependence of TH17 cell differentiation.

Author

Bergamini, Giovanna, Bell, Kathryn, Shimamura, Satoko, Werner, Thilo, Cansfield, Andrew, Müller, Katrin, Perrin, Jessica, Rau, Christina, Ellard, Katie, Hopf, Carsten, Doce, Carola, Leggate, Daniel, Mangano, Raffaella, Mathieson, Toby, O'Mahony, Alison, Plavec, Ivan, Rharbaoui, Faiza, Reinhard, Friedrich, Savitski, Mikhail M, and Ramsden, Nigel

Subjects
CELL differentiation, LIPID metabolism, PHOSPHOINOSITIDES, AUTOIMMUNE diseases, CHEMICAL biology
Abstract

We devised a high-throughput chemoproteomics method that enabled multiplexed screening of 16,000 compounds against native protein and lipid kinases in cell extracts. Optimization of one chemical series resulted in CZC24832, which is to our knowledge the first selective inhibitor of phosphoinositide 3-kinase ? (PI3K?) with efficacy in in vitro and in vivo models of inflammation. Extensive target- and cell-based profiling of CZC24832 revealed regulation of interleukin-17-producing T helper cell (TH17) differentiation by PI3K?, thus reinforcing selective inhibition of PI3K? as a potential treatment for inflammatory and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Published
2012
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21. Affinity for the cognate monoclonal antibody of synthetic peptides derived from selection by phage display.

Author

Ferrieres, Gaelle, Villard, Sylvie, Pugniere, Martine, Mani, Jean-Claude, Navarro-Teulon, Isabelle, Rharbaoui, Faiza, Laune, Daniel, Loret, Erwann, Pau, Bernard, and Granier, Claude

Subjects
PEPTIDES, PROTEIN affinity labeling, MONOCLONAL antibodies, AMINO acid sequence, ANALYTICAL chemistry
Abstract

Examines the affinity labeling of cognate monoclonal antibody 11E12 (mAb 11E12) of synthetic peptide sequences on cellulose membranes. Phage binding analysis; Identification of critical residues of native peptide epitope of mAb 11E12; Circular dichroism spectra of synthetic peptides.

Published
2000

22. The Mycoplasma-Derived Macrophage-Activating 2-Kilodalton Lipopeptide Triggers Global Immune Activation on Nasal Mucosa-Associated Lymphoid Tissues

Author

Rharbaoui, Faiza, Westendorf, Astrid, Link, Claudia, Felk, Sandra, Buer, Jan, Gunzer, Matthias, and Guzmán, Carlos A.

Abstract

ABSTRACTA better knowledge on how immune responses are initiated in mucosal tissues would facilitate the design of new mucosal vaccines, as well as improve our understanding on host defense against infection. We investigated the mechanisms of adjuvanticity of the Mycoplasma-derived macrophage-activating 2-kDa lipopeptide (MALP-2), which binds to the heterodimer formed by the Toll-like receptors 2 and 6 (TLR2 and -6), at the level of the murine nasal mucosa-associated lymphoid tissues (NALT). TLR2 expression analysis demonstrated that several cell types from the nasal cavity were able to overexpress this receptor, either constitutively (such as B cells) or after stimulation (i.e., T cells). MALP-2 stimulated a strong B-cell activation. In addition, the antigen presentation capacity of dendritic cells was improved after in vivo loading with antigen in the presence of MALP-2. We also observed an up-regulated expression of activation markers and adhesion molecules on T cells, suggesting that they have enhanced responsiveness and interaction potential. Quantitative reverse transcription-PCR analysis showed that MALP-2 administration resulted in the stimulation of a proinflammatory cascade. We observed an early up-regulated expression of IP-10, MCP-1, MCP-3, MIP-1α, MIP-2, and CCR-2 which was reversed within 36 h. The obtained results demonstrated that MALP-2 creates a reversible local microenvironment which promotes effective priming of T and B cells in the NALT.

Published
2004
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23. Characterization of a Novel Intracellularly Activated Gene from Salmonella entericaSerovar Typhi

Author

Basso, Holger, Rharbaoui, Faiza, Staendner, Lothar H., Medina, Eva, García-Del Portillo, Francisco, and Guzmán, Carlos A.

Abstract

ABSTRACTA Salmonella entericaserovar Typhi gene that is selectively up-regulated upon bacterial invasion of eukaryotic cells was characterized. The open reading frame encodes a 298-amino-acid hydrophobic polypeptide (30.8 kDa), which is predicted to be an integral membrane protein with nine membrane-spanning domains. The protein is closely related (87 to 94% reliability) to different transport and permease systems. Gene expression under laboratory conditions was relatively weak; however, sevenfold induction was observed in a high-osmolarity medium (300 mM NaCl). The growth pattern in a laboratory medium of a serovar Typhi strain Ty2 derivative containing a 735-bp in-frame deletion in this gene, named gaiA(for gene activated intracellularly), was not affected. In contrast, the mutant was partially impaired in intracellular survival in murine peritoneal macrophages, as well as in human monocyte-derived macrophages. However, in the case of human macrophages, this survival defect was modest and evident only at late infection times (24 h). Despite the distinct intracellular survival kinetics displayed in macrophages of different species, the gaiAnull mutant was significantly affected in its potential to trigger apoptosis in both murine and human macrophages. Provision of the gaiAgene in transresulted in complementation of these phenotypes. Interestingly, the absence of a functional gaiAgene caused a marked attenuation in the mouse mucin model, as shown by the increase (3 orders of magnitude) in the 50% lethal dose of the mutant strain over that of the parental strain Ty2 (P≤ 0.05). Altogether, these data indicate that the product encoded by the gaiAgene is required for triggering apoptosis and bacterial survival within murine macrophages, which is consistent with the in vivo results obtained in the mouse mucin model. However, gaiAwas not required for initial intracellular survival in human cells, indicating that its role in the natural host might be more complex than is suggested by the studies performed in the murine system.

Published
2002
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