DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8,796,427 B2 Spee Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8,796,427 B2 Spee Et Al USOO8796427B2 (12) United States Patent (10) Patent No.: US 8,796,427 B2 Spee et al. (45) Date of Patent: Aug. 5, 2014 (54) HUMANIZED ANTI-HUMAN NKG2A EP 1036327 A2 9, 2000 MONOCLONAL ANTIBODY JP O3112485 A 5, 1991 JP O3112486 A 5, 1991 (75) Inventors: Petrus Johannes Louis Spee, Allerød E. 2025. A 3.28. (DK); Jianhe Chen, Beijing (CN); JP O3112484 U. 8, 2005 Soren Berg Padkjaer, Vaerlose (DK); WO 99.28748 A2 6, 1999 Jing Su, Beijing (CN); Jinchao Zhang, W 94.9. A2 258 Beijing (CN); Jiujiu Yu, Zhejiang (CN) WO O3,OO8449 A1 1, 2003 WO O3,O95965 A2 11/2003 (73) Assignee: Novo Nordisk A/S, Bagsvaerd (DK) WO 2004.?003.019 A2 1/2004 WO WO-2004/056312 T 2004 (*) Notice: Subject to any disclaimer, the term of this WO WO 2006/070286 12, 2004 patent is extended or adjusted under 35 W. 3:39:23, A. i58. U.S.C. 154(b) by 153 days. WO WO 2006O70286 A2 * T 2006 WO 2007042573 A2 4/2007 (21) Appl. No.: 12/811,990 WO WO 2007042573 A2 * 4, 2007 WO WO 2008/OO9545 1, 2008 (22) PCT Filed: Jan. 23, 2009 WO 2009/092805 A1 T 2009 (86). PCT No.: PCT/EP2009/050795 OTHER PUBLICATIONS S371 (c)(1), Petrie, E. J., et al. (2008), J. Exp. Med. 205: 725-735.* (2), (4) Date: Nov. 19, 2010 Bagot et al., “Functional Inhibitory Receptors Expressed by a Cuta neous T-Cell Lymphoma-Specific Cytolytic Clonal T-Cell Popula (87) PCT Pub. No.: WO2009/0928.05 tion.” Journal ofInvestigative Dermatology, 2000, vol. 115, No. 6,pp. 994-999. PCT Pub. Date: Jul. 30, 2009 Bagot et al., “CD4+ Cutaneous T-Cell Lymphoma Cells Express the p140-Killer Cell Immunoglobulin-like Receptor.” Blood, 2001, vol. (65) Prior Publication Data 97, No. 5, pp. 1388-1391. US 2011 FOOS2606A1 Mar. 3, 2011 Biassoni et al., "Molecular and Functional Characterization of NKG2D, NKp80, and NKG2C Triggering NK Cell Receptors in Rhesus and Cynomolgus Macaques: Monitoring of NK Cell Func Related U.S. Application Data tion During Simian HIV Infection.” Journal of Immunology, 2005, (60) Provisional application No. 61/025,923, filed on Feb. vol. 174, pp. 5695-5705. 4, 2008. Carretero et al., “The CD94 and NKG2-AC-type Lectins Covalently Assemble to FormaNatural Killer Cell Inhibitory Receptor for HLA (30) Foreign Application Priority Data Class I Molecules.” European Journal of Immunology, 1997, vol.27, pp. 563-567. Costa et al., “Differential Disappearance of Inhibitory Natural Killer Jan. 24, 2008 (EP) ..................................... O81506O1 Cell Receptors during HAART and Possible Impairment of HIV-1- Specific CD8 Cytotoxic T Lymphocytes.” AIDS, 2001, vol. 15, pp. (51) Int. Cl. 965-974 C07K 6/28 (2006.01) Haedicke et al., “Expression of CD94/NKG2A and Killer (52) U.S. Cl. Immunoglobulin-Like Receptors in NK Cells and a Subset of CPC ......... C07K 16/2851 (2013.01); C07K 2317/76 Extranodal Cytotoxic T-cell Lymphomas.” Blood, 2000, vol. 95, No. (2013.01); C07K 23.17/33 (2013.01) 11, pp. 3628-3630. USPC ..................................................... S30/388.22 Kamarashev et al., “Differential Expression of Cytotoxic Molecules (58) Field of Classification Search and Killer Cell Inhibitory Receptors in CD8+ and CD56+ Cutaneous None Lymphomas.” American Journal of Pathology, 2001, vol. 158, No. 5, See application file for complete search history. pp. 1593-1598. (Continued) (56) References Cited U.S. PATENT DOCUMENTS Primary Examiner — Zachary Skelding (74) Attorney, Agent, or Firm — Saliwanchik, Lloyd & 5,489,525 A 2f1996 Pastan Eisenschenk 5,876,950 A 3, 1999 Siadak et al. 5,994,524 A 11/1999 Matsushima et al. 8,206,709 B2 6/2012 Spee et al. 2003/0095965 A1 5, 2003 Van Beneden et al. (57) ABSTRACT 2005, 0037002 A1 2/2005 Velardi et al. 2009, 0208416 A1 8, 2009 Moretta et al. The present invention relates to agents that are non-competi 2011/0052606 A1 3/2011 Spee et al. tive antagonists of the CD94/NKG2A receptor such as certain 2011/0229486 A1 9, 2011 Moretta et al. anti-NKG2A antibodies, in particular humanized versions of murine anti-NKG2A antibody Z199, as well as methods of FOREIGN PATENT DOCUMENTS producing and using Such agents and antibodies. CN 1747969. A 3, 2006 CN 101107269. A 1, 2008 6 Claims, 10 Drawing Sheets US 8,796.427 B2 Page 2 (56) References Cited Instructions to Authors, European Journal of Immunology, pp. 1-6, 2009. OTHER PUBLICATIONS Gavilondo et al., “Antibody Engineering at the Millennium.” Biotechniques, 2000, vol. 29, No. 1, pp. 128-145. Le Bouteiller et al., “Engagement of CD160 Receptor by HLA-C is a Moretta et al., Identification of Four Subsets of Human CD3-CD16+ Triggering Mechanism used by Circulating Natural Killer (NK) Cells Natural Killer (NK) Cells by the Expression of Clonally Distributed Functional Surface Molecules: Correlation between Subset Assign to Mediate Cytotoxicity.” Proceedings of the National Academy of ment of NK Clones and Ability to Mediate Specific Alloantigen Sciences in the USA, 2002, vol. 99, No. 26, pp. 16963-16968. Recognition, J. Exp. Med., 1990, vol. 172, pp. 1589-1598. Mavilio et al., “Identification of NKG2A and NKp80 as Specific Cleland et al., “The Development of Stable Protein Formulations: A Natural Killer Cell Markers in Rhesus and Pigtailed Monkeys.” Close Look at Protein Aggregation, Deamidation, and Oxidation.” Blood, 2005, vol. 106, No. 5, pp. 1718-1725. Critical Reviews in Therapeutic Drug Carrier Systems, 1993, vol. 10, Mingarietal. “HLA Class I-specific Inhibitory Receptors in Human No. 4, pp. 307-377. T Lymphocytes: Interleukin 15-induced Expression of CD94/ Sablitzky et al., “Molecular Basis of an Isogenic Anti-Idiotypic NKG2A in Superantigen- or Alloantigen-activiated CD8+ T Cells.” Response.” The EMBO Journal, 1984, vol. 3, No. 12, pp. 3005-3012. Proceedings of the National Academy of Sciences of the USA, 1998, Casset et al., Biochemical and Biophysical Research Communica vol. 95, pp. 1172-1177. tions, “A Peptide Mimetic of an Anti-CD4 Monoclonal Antibody by Ponte, et al., “Inhibitory Receptors Sensing HLA-G1 Molecules in Rational Design”, 2003, vol. 307, pp. 198-205. Pregnancy: Decidual-associated Natural Killer Cells Express LIR-1 Chenet al., Journal of Molecular Biology. “Selection and Analysis of and CD94/NKG2A and Acquire p49, and HLA-G1-Specific Recep an Optimized Anti-Vegf Antibody: Crystal Structure of an Affinity tor.” Proceedings of the National Academy of Sciences of the USA, Matured FAB in Complex With Antigen”, 1999, vol. 293, pp. 865 1999, vol. 96, pp. 5674-5679. 881. Sivori et al., “CD94 Functions as a Natural Killer Cell Inhibitory De Pascalis et al., Journal of Immunology, “Grafting of "Abbrevi Receptor for Different HLA Class I Alleles: Identification of the ated” Complementarity—Determining Regions Containing Speci Inhibitory Form of CD94 by the Use of Novel Monoclonal Antibod ficity-Determining Residues Essential for Ligand Contact to Engi ies.” European Journal of Immunology, 1996, vol. 26, pp. 2487-2492. neer a Less Immunogenic Humanized Monoclonal Antibody', 2002, Sivori et al., “p46, a Novel Natural Killer Cell-specific Surface Mol vol. 169, pp. 3076-3084. ecule that Mediates Cell Activation.” Journal of Experimental Medi Gonzales Noreen E et al. Tumor Biology, “Minimizing the cine, 1997, vol. 186, No. 7, pp. 1129-1136. Immunogenicity of Antibodies for Clinical Application', 2005, vol. Vacca et al., “Analysis of Natural Killer Cells Isolated from Human 26, No. 1, pp. 31-43. Decidua: Evidence that 2B4 (CD244) Functions as an Inhibitory Holm et al., Molecular Immunology, “Functional Mapping and Receptor and Blocks NK-cell Function.” Blood, 2006, vol. 108, No. Single Chain Construction of the Anti-Cytokeratin 8 Monoclonal 13, pp. 4078-4085. Antibody TS1’, 2007, vol. 44, pp. 1075-1084. Vitale et al., “The Leukocyte Ig-like Receptor (LIR)-1 for the Kashmiri et al., Methods, "SDR Grafting A New Approach to Cytomegalovirous UL18 Protein Displays a Broad Specificity for Antibody Humanization', 2005, vol. 36, No. 1, pp. 25-34. Different HLA Class I Alleles: Analysis of LIR-1+NK Cell Clones.” Kumar et al., Journal of Biological Chemistry, “Molecular Cloning International Immunology, 1999, vol. 11, No. 1, pp. 29-35. and Expression of the FABs of Human Autoantibodies in Escherichia Voss et al., “Participation of the CD94 Receptor Complex in coli, 2000, vol. 275, pp. 35129-35136. Costimulation of Human Natural Killer Cells,” Journal of Immunol MacCallumet al., Journal of Molecular Biology. "Antibody-Antigen ogy, 1998, vol. 160, pp. 1618-1626. Interactions: Contact Analysis and Binding Site Topography”, 1996, Zimmer et al., “Activity and Phenotype of Natural Killer Cells in vol. 262, pp. 732-745. Peptide Transporter (TAP)-deficient Patients (Type I Bare Lympho Rudikoffet al., Proceedings of the National Academy of Sciences of cyte Syndrome),” Journal of Experimental Medicine, 1998, vol. 187. the USA, "Single Amino Acid Substitution Altering Antigen-Binding No. 1, pp. 117-122. Specificity”, 1982, vol. 79, pp. 1979-1983. Castriconi et al., “Shaping of Adaptive Immunity by Innate Interac Smith-Gill et al., Journal of Immunology, "Contributions of tions.” C.R. Biologies, 2004, vol. 327, pp. 533-537. Immunoglobulin Heavy and Light Chains to Antibody Specificity for Guma et al., “Imprint of Human Cytomegalovirus Infection on the Lysozyme and Two Haptens”, 1987, vol. 139, pp. 4135-4144. NK Cell Receptor Repertoire.” Blood, 2004, vol. 104, No. 12, pp. Song et al., Biochemical and Biophysical Research Communica 3664-3671. tions, “Light Chain of Natural Antibody Plays a Dominant Role in Gunturi et al., “The Role of CD94/NKG2 in Innate and Adaptive Proten Antigen Binding”, 2000, vol. 268, pp. 390-394. Immunity.” Immunologic Research, 2004, vol. 30, No. 1, pp. 29-34. Vajdos et al., Journal of Molecular Biology. “Comprehensive Func Jinushi et al., “Negative Regulation of NK Cell Activities by Inhibitor tional Maps of the Antigenbiding Site of an Anti-ERBB2 Antibody Receptor CD94/NKG2A Leads to Altered NK Cell-Induced Modu Obtained With Shotgun Scanning Mutagenesis', 2002, vol.
Load more

Recommended publications
  • Citrullinated Protein Antibody Paratope Drives Epitope Spreading and Polyreactivity in Rheumatoid Arthritis
    Arthritis & Rheumatology Vol. 0, No. 0, Month 2019, pp 1–11 DOI 10.1002/art.40760 © 2019, American College of Rheumatology Affinity Maturation of the Anti–Citrullinated Protein Antibody Paratope Drives Epitope Spreading and Polyreactivity in Rheumatoid Arthritis Sarah Kongpachith, Nithya Lingampalli, Chia-Hsin Ju, Lisa K. Blum, Daniel R. Lu, Serra E. Elliott, Rong Mao and William H. Robinson Objective. Anti–citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA). While epitope spreading of the serum ACPA response is believed to contribute to RA pathogenesis, little is understood regarding how this phenomenon occurs. This study was undertaken to analyze the antibody repertoires of individuals with RA to gain insight into the mechanisms leading to epitope spreading of the serum ACPA response in RA. Methods. Plasmablasts from the blood of 6 RA patients were stained with citrullinated peptide tetramers to identify ACPA- producing B cells by flow cytometry. Plasmablasts were single-cell sorted and sequenced to obtain antibody repertoires. Sixty-nine antibodies were recombinantly expressed, and their anticitrulline reactivities were characterized using a cyclic citrullinated peptide enzyme- linked immuosorbent assay and synovial antigen arrays. Thirty- six mutated antibodies designed either to represent ancestral antibodies or to test paratope residues critical for binding, as determined from molecular modeling studies, were also tested for anticitrulline reactivities. Results. Clonally related monoclonal ACPAs and their shared ancestral antibodies each exhibited differential re- activity against citrullinated antigens. Molecular modeling identified residues within the complementarity-determining region loops and framework regions predicted to be important for citrullinated antigen binding. Affinity maturation re- sulted in mutations of these key residues, which conferred binding to different citrullinated epitopes and/or increased polyreactivity to citrullinated epitopes.
    [Show full text]
  • Neural Message Passing for Joint Paratope-Epitope Prediction
    Neural message passing for joint paratope-epitope prediction Alice Del Vecchio 1 Andreea Deac 2 3 4 Pietro Lio` 1 Petar Velickoviˇ c´ 4 Abstract Hence, both the antibody and the antigen may be viewed as sequences of amino acid residues. Their binding site Antibodies are proteins in the immune system consists of two regions: the paratope on the antibody, and which bind to antigens to detect and neutralise the epitope on its corresponding antigen. Predicting them them. The binding sites in an antibody-antigen can therefore be posed as a binary classification problem: interaction are known as the paratope and epitope, for each amino acid residue in the antibody and antigen, respectively, and the prediction of these regions respectively, do they participate in the binding? is key to vaccine and synthetic antibody develop- ment. Contrary to prior art, we argue that paratope However, proteins can also be considered as graphs with its and epitope predictors require asymmetric treat- residues as nodes, with two nodes sharing an edge if their ment, and propose distinct neural message passing residues are spatially close. Recently, such contact graphs architectures that are geared towards the specific have been directly leveraged for protein function prediction aspects of paratope and epitope prediction, re- by Gligorijevic et al.(2020). spectively. We obtain significant improvements The advantage of considering a sequence based approach on both tasks, setting the new state-of-the-art and over a graph-based approach is that structural information recovering favourable qualitative predictions on is much harder to obtain. However, recent advancements antigens of relevance to COVID-19.
    [Show full text]
  • Antigen Mimicry-Recognizing Paratope
    Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen−Antibody Interactions Manifests in Molecular Mimicry This information is current as of September 28, 2021. Suman Tapryal, Vineet Gaur, Kanwal J. Kaur and Dinakar M. Salunke J Immunol published online 3 June 2013 http://www.jimmunol.org/content/early/2013/06/01/jimmun ol.1203260 Downloaded from Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 28, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published June 3, 2013, doi:10.4049/jimmunol.1203260 The Journal of Immunology Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry Suman Tapryal,*,1 Vineet Gaur,*,1 Kanwal J. Kaur,* and Dinakar M. Salunke*,† Molecular mimicry manifests antagonistically with respect to the specificity of immune recognition. However, it often occurs because different Ags share surface topologies in terms of shape or chemical nature.
    [Show full text]
  • IMMUNOCHEMICAL TECHNIQUES Antigens Antibodies
    Imunochemical Techniques IMMUNOCHEMICAL TECHNIQUES (by Lenka Fialová, translated by Jan Pláteník a Martin Vejražka) Antigens Antigens are macromolecules of natural or synthetic origin; chemically they consist of various polymers – proteins, polypeptides, polysaccharides or nucleoproteins. Antigens display two essential properties: first, they are able to evoke a specific immune response , either cellular or humoral type; and, second, they specifically interact with products of this immune response , i.e. antibodies or immunocompetent cells. A complete antigen – immunogen – consists of a macromolecule that bears antigenic determinants (epitopes) on its surface (Fig. 1). The antigenic determinant (epitope) is a certain group of atoms on the antigen surface that actually interacts with the binding site on the antibody or lymphocyte receptor for the antigen. Number of epitopes on the antigen surface determines its valency. Low-molecular-weight compound that cannot as such elicit production of antibodies, but is able to react specifically with the products of immune response, is called hapten (incomplete antigen) . antigen epitopes Fig. 1. Antigen and epitopes Antibodies Antibodies are produced by plasma cells that result from differentiation of B lymphocytes following stimulation with antigen. Antibodies are heterogeneous group of animal glycoproteins with electrophoretic mobility β - γ, and are also called immunoglobulins (Ig) . Every immunoglobulin molecule contains at least two light (L) and two heavy (H) chains connected with disulphidic bridges (Fig. 2). One antibody molecule contains only one type of light as well as heavy chain. There are two types of light chains - κ and λ - that determine type of immunoglobulin molecule; while heavy chains exist in 5 isotypes - γ, µ, α, δ, ε; and determine class of immunoglobulins - IgG, IgM, IgA, IgD and IgE .
    [Show full text]
  • Immunoglobulins.Pdf
    Immunoglobulins RAKESH SHARDA Department of Veterinary Microbiology NDVSU College of Veterinary Science & A.H., MHOW Structure and Functions Definition • Immunoglobulins are glycoprotein molecules belonging to γ-globulins class of plasma proteins produced in response to a non-self or an altered self immunogen and act as antibodies in humoral adaptive immune response. • Immunoglobulins are produced in vertebrates by plasma cells, which are the terminally differentiated B lymphocytes + - albumin globulins α α β γ Amount of protein of Amount 1 2 Immune serum Ag adsorbed serum Mobility Basic Immunoglobulin Structure • γ-globulin • glycoprotein • heterodimer • ‘Y’ shaped molecule • coded by immunoglobulin supergene family Basic Immunoglobulin Structure Disulfide bond Carbohydrate C V L L CH CH CH 2 3 V 1 Hinge Region H Immunoglobulin Structure – a monomer (H2L2) Disulfide bond • 2 Heavy & 2 Light chains Carbohydrate • Disulfide bonds CL – Inter-chain VL CH2 CH3 – Intra-chain CH1 Hinge Region VH Immunoglobulin Structure • Variable & Constant Disulfide bond regions in each chain – VL & CL Carbohydrate – VH & CH C • Forms globular loop L like structure called as VL CH2 CH3 domains CH1 Hinge Region • Hinge Region VH Basic Immunoglobulin Structure • A monomer (H2L2) of an immunoglobulin molecule is made up of: – 2 Light Chains (identical) ~25 KDa – 2 Heavy Chains (identical) ~50 KDa • Each light chain bound to heavy chain by disulfide bonds (H-L) • Each heavy chain bound to heavy chain by disulfide bonds (H-H) • The ¼ portion of each H chain and ½ of each L chain towards amino terminal are more variable (110 aa each - VH and VL) in amino acid composition as compared to the remaining portion towards carboxyl terminal (CH and CL) in each monomer, which has nearly constant composition in each domain of a given isotype.
    [Show full text]
  • A Case Report of Nephrotic Syndrome While Undergoing Quinine Therapy
    Open Access Case Report DOI: 10.7759/cureus.2283 A Case Report of Nephrotic Syndrome While Undergoing Quinine Therapy Brittany Albrecht 1 , Shelley Giebel 2 , Michelle McCarron 3 , Bhanu Prasad 2 1. College of Medicine, University of Saskatchewan 2. Department of Nephrology, Regina General Hospital 3. Research and Performance Support, Saskatchewan Health Authority Corresponding author: Brittany Albrecht, [email protected] Abstract We summarize the case of an 81-year-old Caucasian female who presented to her family physician with signs and symptoms of nephrotic syndrome following a brief exposure to quinine. Prior to that visit, she was clinically well with no chronic medical ailments and met with her family physician for annual physical assessments. She had taken 11 tablets of quinine for nocturnal leg cramps over the course of 28 days before starting to notice mild peripheral edema, which subsequently progressed, leading to a family physician review. Her initial serum albumin level was 12 g/L, and a 24-hour urine protein output was quantified at 8.14 g/day; she was diagnosed as having nephrotic syndrome. A kidney biopsy confirmed the diagnosis of minimal change disease (MCD). Quinine therapy was stopped, and she was initiated on a tapering regime of prednisone with concurrent cyclosporine therapy. Within a fortnight of starting therapy, she went into remission and her immunosuppressive medications were rapidly tapered and discontinued. This paper reports an association between the use of quinine and subsequent MCD. This case report proposes that the use of quinine has an association with, and may be causal for, the development of minimal change disease.
    [Show full text]
  • 4 Antibodies from Other Species Melissa L
    85 4 Antibodies from Other Species Melissa L. Vadnais1, Michael F. Criscitiello2, and Vaughn V. Smider1 1Department of Molecular Medicine, The Scripps Research Institute, 10550 N. Torrey Pines, La Jolla, CA 92037, USA 2Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, Department of Veterinary Pathobiology, 400 Raymond Stotzer Parkway, College Station, TX 77843, USA 4.1 Introduction Immunoglobulins are the molecular basis of humoral immunity. Across different species, these macromolecules maintain a common quaternary structure, which is typically comprised of two identical heavy chains with covalently attached oligosaccharide groups and two identical non-glycosylated, light chains. These glycoprotein molecules recognize and bind a particular antigen in a highly complex and exceedingly specific immune response. Antibodies are the primary protective molecules elicited by most vaccines, and recombinant antibodies are now a major class of therapeutics for multiple diseases. The earliest antibody therapeutics were derived from serum of nonhuman species. In particular, horse serum served as anti-venom yet had substantial toxicity (serum sickness) due totheimmuneresponseagainstthenonhumanantibodyprotein[1,2].Other antibody preparations such as anti-thymocyte globulin produced in rabbit had therapeutic benefit but also had significant toxicity. The use of alternative species for these therapeutic preparations was largely due to ease of production, as they were developed prior to the advent of modern molecular biology techniques, which have enabled rapid discovery and engineering of recombinant antibodies. Thus, most current approaches for producing recombinant antibodies rely on humanizing antibodies derived from other species, usually mice, or beginning with human scaffolds engineered into libraries or transgenic “humanized” mice. Recently, however, novel features of antibodies derived from other species have sparked interest in developing antibodies that may have particular unique features in binding certain antigens or epitopes [3–7].
    [Show full text]
  • Monoclonal Immunoglobulin
    Chapter 2 Monoclonal Immunoglobulin Marie-Christine Kyrtsonis, Efstathios Koulieris, Vassiliki Bartzis, Ilias Pessah, Eftychia Nikolaou, Vassiliki Karalis, Dimitrios Maltezas, Panayiotis Panayiotidis and Stephen J. Harding Additional information is available at the end of the chapter http://dx.doi.org/10.5772/55855 1. Introduction Secretion of monoclonal immunoglobulins (M-Ig) may be associated with several malignant conditions, also called M-protein, paraprotein, or M-component they are produced by an abnormally expanded single (‘’mono-‘’) clone of plasma cells in an amount that can be detected in serum, urine, or rarely in other body fluids [1]. The M-Ig can be an intact immunoglobulin (Ig) (containing both heavy and light chains), or light chains in the absence of heavy chain (encountered in light chain myeloma, light chain deposition disease, AL amyloidosis), or rarely heavy chains in the absence of light chains only (heavy chain disease). All intact Igs have the same structure, made up of mirror imaged identical light and heavy chains. There are five classes of heavy chain, γ, α, μ, δ and ε with two classes of light chain κ and λ. Igs are secreted by terminally differentiated B-lymphocytes and their normal function is to act as antibodies recognizing a specific antigen. During B-cell maturation, the rearrangement of Ig heavy and light chain genes takes place early in pre-B-cell development and ends in memory B-cells or Ig producing plasma cells that have a unique heavy and light chain gene rearrangement, thus being selected to recognize a given antigen. During, oncogenic events which occur randomly during this process, the B cell may acquire a survival advantage, and proliferate into identical (clonal) daughter B-cells able to differentiate into Ig producing cells secreting a monoclonal component.
    [Show full text]
  • Brief History of Important Immunologic Discoveries and Developments
    Brief History of Important Immunologic Discoveries and Developments Year Event Author(s) 1798 Cowpox vaccination Edward Jenner 1866 Wound disinfection Joseph Lister 1876 Discovery of B. antracis, foundation of Robert Koch bacteriology 1880 Discovery of attenuated vaccine by Louis Pasteur invitro passages 1883 Phagocytosis, cellular immunity theory Elie I. I. Metchnikoff 1888 Discovery of bacterial toxins P. P. Emile Roux and Alexandre E. J. Y ersin 1890 Discovery of antitoxins, foundation of Emil A. von Behring and serotherapy Shibasaburo Kitasato 1894 Immunologic bacteriolysis Richard F. J. Pfeiffer and Vasily I. Isaeff 1894 Discovery of antibody and complement Jules J.B. V. Bordet activity as the active factors in bacteriolysis 1896 Discovery of specific agglutination Herbert E. Durham and Max von Gruber 1896 Agglutination test for the diagnosis of Georges F. I. Widal and typhoid (Widal test) Jean-Marie-Athanase Sicard 1900 Formulation of side-chain theory of anti- Paul Ehrlich body formation 1900 Discovery of A, B, 0 blood groups Karl Landsteiner 1900 Development of complement fixation Jules J.B. V. Bordet and reaction Octave Gengou 1902 Discovery of anaphylaxis Charles R. Richet and Paul Portier 1903 Local anaphylaxis due to antibody- Nicholas M. Arthus antigen complex: Arthus reaction 1903 Discovery of opsonization Almroth E. Wright and Steward R. Douglas 440 Brief History of Important Immunologic Discoveries and Developments Year Event Author(s) 1905 Description of serum sickness Clemens von Pirquet and Bela Schick 1910 Introduction of salvarsan, later neo- Paul Ehrlich and Sahachiro Hata salvarsan, foundation of chemotherapy of infections 1910 Development of anaphylaxis test William Schultz (Schultz-Dale) 1914 Formulation of genetic theory of tumor Clarence C.
    [Show full text]
  • Anti-Idiotype Antibodies: Powerful Tools for Antibody Drug Development
    Anti-Idiotype Antibodies: Powerful Tools for Antibody Drug Development Michelle Parker, Ph.D. [email protected] Table of Contents 1 What is an Anti-Idiotype Antibody? 2 Anti-Idiotype Antibody Applications 3 Obstacles & Solutions to the Generation of Anti-Idiotype Abs 4 Downstream Assay Development 5 Features of GenScript’s Anti-Idiotype Antibody Services 6 GenScript Anti-Idiotype Antibody Packages Make Research Easy 2 Antibody: Structure and Function Antibody (Ab): Recognition proteins found in the serum and other bodily fluids of vertebrates that react specifically with the antigens that induced their formation. Overall structure: • 2 identical light chains (blue) • 2 identical heavy chains (green/purple) Variable regions and constant regions 5 classes of Abs: • IgG, IgA, IgM, IgD, IgE • All contain either λ or κ light chains • Biological effector functions are mediated by the C domain Chemical structure explains 3 functions of Abs: 1. Binding versatility 2. Binding specificity 3. Biological activity Make Research Easy 3 Antibody Binding Regions Idiotope – the antigenic determinants in or close to the variable portion of an antibody (Ab) Paratope – the part of an Ab that recognizes an antigen, the antigen-binding site of an Ab or complementarity determining region (CDR) Epitope – the part of the antigen to which the paratope binds Make Research Easy 4 Anti-Idiotype Antibodies Anti-idiotype antibodies (Anti-IDs) – Abs directed against the paratope (or CDR region) of another Ab Hypervariable regions (or the idiotype
    [Show full text]
  • Determination of the Rituximab Binding Site to the CD20 Epitope
    Determination of the Rituximab Binding Site to the CD20 Epitope Using SPOT Synthesis and Surface Plasmon Resonance Analyses Laure Bar, Christophe Nguyen, Mathieu Galibert, Francisco Santos-Schneider, Gudrun Aldrian, Jérôme Dejeu, Rémy Lartia, Liliane Coche-Guérente, Franck Molina, Didier Boturyn To cite this version: Laure Bar, Christophe Nguyen, Mathieu Galibert, Francisco Santos-Schneider, Gudrun Aldrian, et al.. Determination of the Rituximab Binding Site to the CD20 Epitope Using SPOT Synthesis and Surface Plasmon Resonance Analyses. Analytical Chemistry, American Chemical Society, In press, 93 (17), pp.6865-6872. 10.1021/acs.analchem.1c00960. hal-03216003 HAL Id: hal-03216003 https://hal.archives-ouvertes.fr/hal-03216003 Submitted on 3 May 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Determination of the rituximab binding site to the CD20 epitope by using SPOT-synthesis and surface plasmon resonance analyses Laure Bar,† Christophe Nguyen,‡ Mathieu Galibert,† Francisco Santos-Schneider,‡ Gudrun Aldrian,‡ Jérôme Dejeu,† Rémy Lartia,† Liliane Coche-Guérente,† Franck Molina,‡ Didier Boturyn*,† †Univ. Grenoble-Alpes, CNRS, DCM UMR 5250, 570 rue de la chimie, CS 40700, 38058 Grenoble Cedex 9, France. Email: [email protected] ‡Sys2Diag, CNRS – ALCEDIAG, Cap delta/Parc Euromédecine, 1682 rue de la Valsière, CS 61003, 34184 Montpellier Cedex 4, France.
    [Show full text]
  • Germline Antibodies Paratope Interactions In
    Adjustable Locks and Flexible Keys: Plasticity of Epitope−Paratope Interactions in Germline Antibodies This information is current as Tarique Khan and Dinakar M. Salunke of October 2, 2021. J Immunol 2014; 192:5398-5405; Prepublished online 30 April 2014; doi: 10.4049/jimmunol.1302143 http://www.jimmunol.org/content/192/11/5398 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2014/04/30/jimmunol.130214 Material 3.DCSupplemental References This article cites 41 articles, 14 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/192/11/5398.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 2, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Adjustable Locks and Flexible Keys: Plasticity of Epitope–Paratope Interactions in Germline Antibodies Tarique Khan*,1 and Dinakar M. Salunke*,† Ag recognition by independent primary Abs against a small flexible Ag with overlapping epitopes was analyzed to address the deter- minants of Ag specificity during the initial encounter.
    [Show full text]