Search

Your search keyword '"Oana I. Lungu"' showing total 5 results
Start Over Author "Oana I. Lungu" Publication Year Range Last 10 years
5 results on '"Oana I. Lungu"'

1. Computer‐based engineering of thermostabilized antibody fragments

Author

Sang Taek Jung, George Georgiou, Chang-Han Lee, Gregory C. Ippolito, Wenzong Li, Jiwon Lee, R. E. Hughes, Oana I. Lungu, Brian Kuhlman, Bryan S. Der, Jeffrey J. Gray, Jianqing Xu, Tae Hyun Kang, Yan Zhang, Nicholas M. Marshall, Bing Tan, Christos S. Karamitros, Andrew D. Ellington, and Aleksandr E. Miklos

Subjects
chemistry.chemical_classification, Environmental Engineering, Molecular model, biology, General Chemical Engineering, Melting temperature, Computer based, Biomolecular engineering, 02 engineering and technology, 021001 nanoscience & nanotechnology, medicine.disease_cause, Article, Antibody fragments, Amino acid, 020401 chemical engineering, chemistry, Biochemistry, medicine, biology.protein, Clostridium botulinum, 0204 chemical engineering, Antibody, 0210 nano-technology, Biotechnology
Abstract

We used the molecular modeling program Rosetta to identify clusters of amino acid substitutions in antibody fragments (scFvs and scAbs) that improve global protein stability and resistance to thermal deactivation. Using this methodology, we increased the melting temperature (T(m)) and resistance to heat treatment of an antibody fragment that binds to the Clostridium botulinum hemagglutinin protein (anti-HA33). Two designed antibody fragment variants with two amino acid replacement clusters, designed to stabilize local regions, were shown to have both higher T(m) compared to the parental scFv and importantly, to retain full antigen binding activity after 2 hours of incubation at 70 °C. The crystal structure of one thermostabilized scFv variants was solved at 1.6 Å and shown to be in close agreement with the RosettaAntibody model prediction.

Published
2019
Full Text
View/download PDF

2. IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Author

Bianca Balbino, George Delidakis, Tae Hyun Kang, Makiko Watanabe, Kendra Triplett, Anja Lux, Navin Varadarajan, Odile Richard-Le Goff, Oana I. Lungu, Pierre Bruhns, George Georgiou, Corrine Alford, Gabrielle Romain, Margaret A. Lindorfer, Wissam Charab, Falk Nimmerjahn, Yan Jessie Zhang, Hidetaka Tanno, Wupeng Yan, Nicholas M. Marshall, Moses Donkor, Chang-Han Lee, Jiwon Lee, Ronald P. Taylor, Biliana Todorova, University of Texas at Austin [Austin], University of Houston, Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Erlangen-Nürnberg [Germany], University of Virginia School of Medicine [US], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), University of Virginia, Department of Biochemistry and Molecular Genetics (xxx), University of Virginia [Charlottesville], We thank Y. Tanno for assistance with protein expression, A. Bui for assistance with liquid chromatography–tandem mass spectrometry, P. Tucker (University of Texas at Austin) for cancer cell lines, D. Lee (MD Anderson Cancer Center) for patient-derived primary acute lymphocytic leukemia cells, the Macromolecular Crystallography Facility of the University of Texas at Austin, the Berkeley Center for Structural Biology, the Advanced Light Source (supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract DE-AC02-05CH11231), the Proteomics Facility at the University of Texas at Austin (supported by grant RP110782 from the Cancer Prevention Research Training Program), and A. Nicola and the Plate-Forme d'Imagerie Dynamique (Institut Pasteur, Paris) for help with the bioluminescence experiments. Supported by the Clayton Foundation, the Institut Pasteur (P.B. laboratory), the Institut National de la Santé et de la Recherche Médicale (P.B. laboratory), the European Research Council Seventh Frame-work Program (ERC-2013-CoG 616050 for the P.B. laboratory), the Pasteur–Paris University International PhD program (B.B.), the Cancer Prevention Research Training Program (RP140108 to M.D., RP160015 to H.T., and RP130570 to N.V.), the American Cancer Society (123506-PF-13-354-01-CDD to N.M.), Uehara Memorial Foundation (H.T.), Japan Society for the Promotion of Science (H.T.), Deutsche Forschungsgemeinschaft (CRC1181-A07 to F.N.), the US National Institutes of Health (R01CA174385 to N.V., and R01 GM104896 to Y.J.Z.) and the Welch Foundation (F-1778 to Y.J.Z.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Cancer Prevention and Research Institute of Texas., European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Virginia, Martin, Marie, and Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples - MYELOSHOCK - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616050 - VALID

Subjects
Cytotoxicity, Immunologic, 0301 basic medicine, Cellular immunity, MESH: Complement C1q, MESH: Immunotherapy, Crystallography, X-Ray, Mass Spectrometry, MESH: Antibodies, Monoclonal, Mice, Tandem Mass Spectrometry, Neoplasms, Immunology and Allergy, MESH: Animals, MESH: Neoplasms, Cytotoxicity, Receptor, MESH: Phagocytosis, MESH: Crystallization, MESH: Immunoglobulin G, biology, Effector, Antibodies, Monoclonal, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Chromatography, Gel, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, 3. Good health, Cell biology, MESH: Surface Plasmon Resonance, Chromatography, Gel, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, Lymphoma, Large B-Cell, Diffuse, Antibody, Crystallization, Lymphoma, B-Cell, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Enzyme-Linked Immunosorbent Assay, In Vitro Techniques, MESH: Receptors, IgG, MESH: Immunoglobulin Fc Fragments, 03 medical and health sciences, Classical complement pathway, Immune system, Phagocytosis, Cell Line, Tumor, Animals, Humans, MESH: Cytotoxicity, Immunologic, MESH: Mice, MESH: Lymphoma, B-Cell, MESH: In Vitro Techniques, MESH: Mass Spectrometry, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, Complement C1q, Receptors, IgG, MESH: Tandem Mass Spectrometry, Surface Plasmon Resonance, MESH: Crystallography, X-Ray, Immunoglobulin Fc Fragments, Complement system, MESH: Burkitt Lymphoma, 030104 developmental biology, Immunoglobulin G, biology.protein, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: Chromatography, Liquid, Chromatography, Liquid
Abstract

International audience; Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.

Published
2017
Full Text
View/download PDF

3. Correction: Corrigendum: Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining

Author

George Georgiou, Scott A. Kerr, Alec B. Rezigh, Itamar Villanueva, Robert A. Davey, Andrew D. Ellington, Amy Altman, Sean M. Carroll, Hidetaka Tanno, Oana I. Lungu, Janelle R. Bentz, Christien Kluwe, Brandon J. DeKosky, Chang-Han Lee, Bo Wang, Jiwon Jung, Erik L. Johnson, and Ann N. Reyes

Subjects
World Wide Web, Immune repertoire, Multidisciplinary, Ebola virus, biology, Computer science, Section (typography), medicine, biology.protein, Antibody, medicine.disease_cause
Abstract

Scientific Reports 5: Article number: 13926; published online: 10 September 2015; updated: 10 June 2016 Hidetaka Tanno and Chang-Han Lee were omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article. The Author Contributions section now reads

Published
2016
Full Text
View/download PDF

4. Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining

Author

Bo Wang, Christien A. Kluwe, Oana I. Lungu, Brandon J. DeKosky, Scott A. Kerr, Erik L. Johnson, Hidetaka Tanno, Chang-Han Lee, Jiwon Jung, Alec B. Rezigh, Sean M. Carroll, Ann N. Reyes, Janelle R. Bentz, Itamar Villanueva, Amy L. Altman, Robert A. Davey, Andrew D. Ellington, and George Georgiou

Subjects
medicine.drug_class, viruses, Immunoglobulin Variable Region, Cross Reactions, Antibodies, Viral, medicine.disease_cause, Monoclonal antibody, Epitope, Virus, Article, Epitopes, Mice, 03 medical and health sciences, 0302 clinical medicine, Antibody Repertoire, medicine, Animals, Humans, 030304 developmental biology, Ebolavirus, B-Lymphocytes, 0303 health sciences, Multidisciplinary, Ebola virus, biology, Hemorrhagic Fever, Ebola, Corrigenda, Virology, 3. Good health, Disease Models, Animal, Phenotype, Immunization, Immunoglobulin G, Antibody Formation, biology.protein, Immunoglobulin Light Chains, Lymph Nodes, Antibody, Immunoglobulin Heavy Chains, Protein Binding, 030215 immunology
Abstract

The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different Ebolaviruses. We developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the VH:VL paired antibody repertoire encoded by highly expanded B cells in the draining popliteal lymph node (PLN). This approach requires neither screening nor selection for antigen-binding. Specifically we show that mouse immunization with Ebola VLPs gives rise to a highly polarized antibody repertoire in CD138+ antibody-secreting cells within the PLN. All highly expanded antibody clones (7/7 distinct clones/animal) were expressed recombinantly and shown to recognize the VLPs used for immunization. Using this approach we obtained diverse panels of antibodies including: (i) antibodies with high affinity towards GP; (ii) antibodies which bound Ebola VLP Kissidougou-C15, the strain circulating in the recent West African outbreak; (iii) non-GP binding antibodies that recognize wild type Sudan or Bundibugyo viruses that have 39% and 37% sequence divergence from Ebola virus, respectively and (iv) antibodies to the Reston virus GP for which no antibodies have been reported.

Published
2015

5. Erratum: Corrigendum: IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Author

Corrine Alford, Gabrielle Romain, Margaret A. Lindorfer, Falk Nimmerjahn, Wissam Charab, Moses Donkor, Navin Varadarajan, George Delidakis, Bianca Balbino, Anja Lux, Hidetaka Tanno, Wupeng Yan, Ronald P. Taylor, Kendra Triplett, Pierre Bruhns, Odile Richard-Le Goff, Chang-Han Lee, Tae Hyun Kang, George Georgiou, Oana I. Lungu, Biliana Todorova, Jiwon Lee, Nicholas M. Marshall, Makiko Watanabe, and Yan Jessie Zhang

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Nat, Effector, Immunology, Immunology and Allergy, Effector functions, Biology, Receptor, Complement (complexity), Cell biology
Abstract

Nat. Immunol.; doi:10.1038/ni.3770; corrected online 27 June 2017 In the version of this article initially published online, the labels identifying each plot in Figure 1b were missing. The labels are as follows (left to right): CHO, FcγRI, FcγRIIaR131, FcγRIIaH131, FcγRIIb, FcγRIIIaF158 and FcγRIIIaV158.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results