Uses of Monoclonal Antibodies

11 Key excerpts on "Uses of Monoclonal Antibodies"

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  Monoclonal Antibodies against Bacteria

  • Alberto Macario(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  The manufacture of large quantities of antibacterial monoclonal anti-bodies for routine and widespread use in many areas (medicine, dentistry, veteri-nary sciences, industry, and biotechnology) is evolving into an industry of its own. The tactics for industrial production with commercial purposes are different from those in basic research. Also research and development endeavors in the Introduction xxiii industrial world differ from research efforts in the academic environment (see Volume II). D. Genetic Engineering Monoclonal antibodies are instrumental in genetic engineering, first to identify useful antigens, for example, those inducing protective immunity, and then to help in the cloning of the genetic codes for these antigens in the preparation of vaccines or diagnostic kits (37,54). E. Biochemistry and Molecular Studies Elucidation of the chemical composition and structure of the antigen molecule bearing the determinant recognized by a monoclonal antibody, and eventually of the determinant itself, should become an important part of chemoimmunotax-onomy and other molecular studies (4,6,10,16,18,23,44,53,54,58,61,65) (see Chapters 1, 6-8, and Volumes II and III). For this purpose, panels of mono-clonal antibodies show extraordinary resolution power, especially if the fine (molecular) specificity of the antibodies is known. In this case, the antibodies constitute a set of high-precision tools for probing molecular markers and for detecting these markers in a variety of materials. One can foresee the occurrence of monoclonal antibodies specific for a marker of a strain, or species, or higher taxon. One can also envisage the use of monoclonal antibodies of predefined mo-lecular specificity for tracing molecular signatures left by a given strain in other microorganisms, subcellular structures (e.g., mitochondria), and materials from ecologic niches, such as fossils and sediments, and from culture superna-tants (see Chapter 11).

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  From Gene to Protein: Translation into Biotechnology

  • Fazal Ahmad(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  Monoclonal Antibodies—Production and Uses Passage contains an image

  MONOCLONAL ANTIBODIES: THE PRODUCTION OF TAILOR-MADE SEROLOGICAL REAGENTS

  Dale E. Yelton, Pallaiah Thammana, Catherine Desaymard, Susan B. Roberts, Sau-Ping Kwan, Angela Giusti, Donald J. Zack, Roberta R. Pollock and Matthew D. Scharff,     Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York U.S.A.

  Publisher Summary

  Immunoassays have been used to detect, quantitate, and localize small amounts of macromolecules in complex biological mixtures. Monoclonal antibodies are chemically defined reagents. Monoclonal antibodies have many benefits over conventional antisera. In addition to providing homogenous reagents that can be generated in large amounts and replenished whenever needed, particular monoclonals can be selected. Once a hybridoma producing a desired antibody has been identified, hundreds of milligrams of that antibody can be generated. These benefits have stimulated investigators, in all areas of biology, to generate monoclonal antibodies against the particular antigen that they are studying. Monoclonal antibodies can also be tailor–made by identifying subclones containing deletions in one or another domain. Such deletion variants have been generated from an IgG2b hybridoma producing antibody that reacts with hapten p-azophenylarsonate. Useful monoclonals can be made even more effective by isolating subclones that have undergone mutations or rearrangements.

  I. INTRODUCTION 

  Immunoassays have been used successfully for years to detect, quantitate, and localize small amounts of macromolecules in complex biological mixtures. While such assays can be made both sensitive and specific, certain properties of conventional antiserums have limited their usefulness, especially for routine diagnosis and therapy. Perhaps the most important of these limitations has been the limited supply of useful antiserum against weak immunogens. This is in part due to the heterogeneity of the immune response which results in each antiserum being a mixture of antibodies with varying affinity, cross reactivities, and effector functions. The particular mix of antibodies or predominance of a subset of antibodies produced by an animal at a certain time in its immune response may be useful for a specified purpose. However, as that mix changes with time or from animal to animal, the nature of the antiserum also changes and it may be impossible to recapture the specificity or other properties again. A second major problem with conventional immunization is that many of the most biologically interesting molecules, such as tumor or differentiation antigens, are small parts of complex mixtures. While specific antiserums can sometimes be generated by extensive and repeated absorption, the heterogeneity and unpredictability of the immune response makes it difficult to repeatedly generate large amounts of antiserum with the same properties. These and other problems with conventional immunization have discouraged and hindered the production of antiserum against many important and useful antigens and have certainly limited the use of immunoassays in the routine diagnostic laboratory to those antigens which can be obtained in relatively pure form and which induce a good immune response.

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  Monoclonal Antibodies

  A Manual of Techniques

  • Heddy Zola(Author)
  • 2013(Publication Date)
  • CRC Press

    (Publisher)

  183 Chapter 7 PROSPECTS, PROBLEMS, AND LIMITATIONS IN THE USE OF MONOCLONAL ANTIBODIES L SCOPE OF THE CHAPTER In the 10 years since a practical method was described for making monoclonal anti­ bodies, the technique has been applied in nearly every field of biology and medicine. Monoclonal antibodies have revolutionized some of the areas in which they have been applied, by providing the reagents with which to analyze the underlying phenomena. The outstanding example is cellular immunology, which has seen the concepts of cel­ lular interactions in the control of immune responses develop in detail and acceptance. The basic concepts existed well before the availability of monoclonal antibodies, but they were based on experiments which were open to criticism because of the lack of specificity of the reagents used. Thus, allo-antisera, used in dissecting cell cooperation in mice, were contaminated with antiviral antibodies, which may or may not have affected the results. In man, experiments on cell cooperation and interaction in the immune response were based on technically difficult in vitro assays which did not re­ produce well in different laboratories. Monoclonal antibodies have provided the probes for identifying and separating cells, enabling the dissection of the mixture of interacting cells which together make the ingredients of the immune response. Having provided the reagents to analyze the im­ mune response at the cellular level, monoclonal antibodies are currently being used to analyze the immune response at a further level of resolution, the molecular level. Mem­ brane receptors for stimulation or suppression are being analyzed and purified, and their functional sites probed with monoclonal antibodies. In this field monoclonal an­ tibodies and probes for DNA and RNA are being used as complementary tools.

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  Nanostructures for Drug Delivery

  • Ecaterina Andronescu, Alexandru Mihai Grumezescu(Authors)
  • 2017(Publication Date)
  • Elsevier

    (Publisher)

  monoclonal antibodies in different databases (Pubmed and Scopus). Athough fewer published articles, the number of publications is constant over the years to Science Direct and Wiley.

  Figure 25.1   Number of Publications by Year/Database

  Mabs are used not only as drugs for treating various diseases, but are also used as powerful tools for a wide range of medical applications. They are routinely used in hospitals for blood type and tissue, a vital process to ensure safe blood transfusion and organ transplantation. In other cases, they are employed as research probes to determine the pathological pathway and the cause of diseases, such as cancer, autoimmune diseases, and neurological disorders. On the diagnostic front, monoclonal antibodies are intrinsic components of test kits for the detection of ovulation, pregnancy, or menopause. They are also used for analyzing body fluids for medical diagnosis, and to determine whether there has been a heart attack.

  Unlike polyclonal antibodies, Mabs are identical antibodies because they are produced by one type of immune cell. Using current hybridoma (mouse/human hybrid cells) technology originally developed by Georges Kohler, Cesar Milstein, and Neils Jerne, Mabs can be produced to bind tightly to virtually any material or antigen, which is defined as a substance that prompts the generation of antibodies that specifically bind to it. Antigens typically consist of proteins or polysaccharides. Epitopes, also known as antigenic determinants, are the part of the antigens through which actual binding to antibodies occurs.

  The Mabs technology allowed scientists to produce huge quantities of pure antibodies aimed at specific selected targets, leading to the design of new diagnostic tests and therapeutics. By injecting a payload of Mabs into the bloodstream, the antibodies were headed straight to their disease target.

  Today, the growth and profitability of Mabs are outstripping those of earlier types of biotechnology drugs and more traditional pharmaceutical ones. Indeed, their expansion is among the fastest in the global pharmaceutical world. In part, this reflects the sector’s embrace of Mabs as an answer to dwindling drugs in the pipeline and reduced revenue streams in the face of the expiration of key patents and the growth of generic medicines.

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  Monoclonal Antibody Technology: The Production and Characterization of Rodent and Human Hybridomas

  • A.M. Campbell(Author)
  • 2000(Publication Date)
  • Elsevier Science

    (Publisher)

  If, in addition, they were obliged to undertake sequential monoclonal antibody production in order to isolate a minor compon- ent of a highly antigenic mixture, the time involved and the running costs would be very extensive. If a single hybridoma line is all that is required then collaborative work with a laboratory with the appropriate facilities and experience would generally be the better course of action. More detailed costing information is given in Chapter 5. Ch. 1 GENERAL PROPERTIES AND APPLICATIONS OF MONOCLONAL ANTIBODIES 17 1.3. Applications of monoclonal antibodies The applications of monoclonal antibody technology are generally outwith the scope of this volume and are reviewed in several others (McMichael and Fabre, 1982; Albertini and Ekins, 1981; Hammer- ling, Hammerling and Kearney, 1981; Kennett, McKearn and Bech- tol, 1980; Edwards, 1981; Yelton and Scharff, 1981). The Index Medicus lists several hundred papers each month under the heading of monoclonal antibodies. It is, however, possible to outline some of the major applications of monoclonal antibody technology at the present time so that the range and scope of the technique may be summarised. 1.3.1. Diagnostic uses Antibodies produced in the mouse or the rat are most commonly used for diagnostic purposes as they are more readily produced. Not only is the fusion frequency an order of magnitude higher but the animal can be hyperimmunised with the chosen antigen. The major advan- tage of monoclonal antibodies over conventional sera in this appli- cation is probably their ready availability for an indefinite period at a standard titre, making direct comparisons between different labora- tories comparatively simple. However, their high specificity has added greatly to the accuracy and speed of the diagnosis. Thus antibodies to common serum analytes such as protein hormones or alphafetopro- tein are already commercially marketed and are slowly replacing conventional sera.

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  Clinical Biochemistry V3

  Contemporary Theories and Techniques

  • Herbert Spiegel(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  3 Monoclonal Antibodies in Clinical Investigations PATRICK C. KUNG, TSE-WEN CHANG, AND VINCENT R. ZURAWSKI, JR. I. Introduction 89 II. Definition and Production of Monoclonal Antibody 91 III. Monoclonal Antibodies for Studying Cell Differentiation and Monitoring Diseases 93 A. Human T-Cell Development Studies 93 B. Pathology and Diagnostic Research using Anti-T-Cell Antibodies 98 C. Monoclonal Antibodies for Diagnosis of Infectious Diseases 101 D. Monoclonal Antibodies Reactive with Tumor-Associated Antigens 104 IV. Monoclonal Antibodies for Serotherapy 106 A. Organ Transplantation 106 B. Treating T- and B-Cell Lymphomas 107 V. In Vitro Treatment of Bone Marrow for Autologous Transplant 108 VI. Monoclonal Antibodies for in Vivo Radioimaging of Tumors. 109 VII. Discussion 110 VIII. Appendix: General Reviews on Perspectives, Methodology, and Applications 111 References 112 I. INTRODUCTION Throughout the history of medicine, technological breakthrough has often brought forth major advances in the diagnosis, monitoring, or thera-peutic intervention of diseases. To date, many diseases, such as cancer, autoimmune disorders, and microbial infections remain difficult to prog-nose or diagnose. In many instances ideal treatment for the disease is still 89 CLINICAL BIOCHEMISTRY Copyright © 1984 by Academic Press, Inc. Contemporary Theories and Techniques, Vol. 3 All rights of reproduction in any form reserved. ISBN 0-12-657103-1 90 Patrick C. Kung, Tse-Wen Chang, and Vincent R. Zurawski, Jr. unavailable. The recent emergence of hybridoma technology for mono-clonal antibody (MOab) production promises some solutions to these medical problems. The antibody molecule is a remarkable product of evolution. The mech-anism of its action was first postulated in the late nineteenth century.

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  Drug Delivery Systems

  • Vasant V. Ranade, John B. Cannon(Authors)
  • 2011(Publication Date)
  • CRC Press

    (Publisher)

  47 2 Site-Specific Drug Delivery Utilizing Monoclonal Antibodies* INTRODUCTION At the beginning of this century, Paul Ehrlich reported the discovery of antibodies. 1 Since that time, many investigators have done extensive work using a wide variety of antibody molecules in immunocytochemistry, radioimmunoassay, and clinical medi-cine. In 1976, Kohler and Milstein employed a method of somatic-cell hybridization in order to successfully generate a continuous “hybridoma” cell line capable of produc-ing monoclonal antibody (MAb) of a defined specificity. 2 Subsequently, several MAbs have exhibited specificity for target sites. It is this property of MAbs that makes them excellent candidates as carriers of therapeutic agents for delivery to specific sites. 3,4 C HEMISTR Y Antibodies are complex proteins, consisting of multiple polypeptide chains that con-tain a variety of reactive chemical groups, such as amino, carboxyl, hydroxyl, and sulfhydryl. Functionally, MAbs possess a molecular polarity based on the joining of an antigen-binding fragment (Fab) to a complement-fixing fragment (Fc). The Fab fragment is responsible for specific antigen binding, whereas the Fc fragment binds to effector cells, fixes complements, and elicits other in vivo biological responses. In order to obtain an MAb suitable for the treatment of human disease, it is neces-sary to maintain both the physical and functional properties of the antibody through-out the steps of production, isolation, purification, and modification. Antibody modification, performed to increase theoretical efficacy, can consist of conjugation of the protein to the following: radionuclides (e.g., 131I and 111In), chemotherapeutic drugs (e.g., methotrexate and vinblastine), and polypeptide toxins (e.g., ricin A chain and polkweed antiviral protein [PAP]). P OLYCLONALS VS . M ONOCLONALS Antibodies can be heterogeneous with respect to size, charge, antigen specificity, and affinity.

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  Chronic Lymphoid Leukemias

  • Bruce D. Cheson(Author)
  • 2001(Publication Date)
  • CRC Press

    (Publisher)

  15 The Use of Therapeutic Monoclonal Antibodies in Chronic Lymphocytic Leukemia MARTIN J. S. DYER* Royal Marsden Hospital , London , England ANDERS OSTERBORG Karolinska Hospital , Stockholm , Sweden I. INTRODUCTION That antibodies have the specificity to deliver targeted therapy for human disease was realized soon after their description in the 1890s (1). The first therapeutic attempts in malignancy were reported in France by Hericourt and Richet as early as 1895 (2). Their conclusion, based on observations made on the effects of crude antisera raised in donkeys and other animals and in patients with advanced disease, was that antibody therapy should be combined with radical surgery, which sounds remarkably modem. Since then, however, therapeutic antibodies have had a long and largely undistinguished history in oncology (3). The introduction of monoclonal antibodies (MAbs) in the 1980s allowed some of the barriers to effective antibody therapy of malignancy to be recognized (4). Furthermore, the advances of genetic engineering and cell culture methods have allowed the almost routine production of large quantities of humanized antibodies (5). Several antibodies have shown considerable potential in a variety of clinical settings, and some of them have now found a routine therapeutic role in oncological practice. Some of the conditions necessary for effective MAb action in vivo and some recent data on the use of CD52 (CAMPATH- 1) and CD20 (Rituximab) MAbs in the treatment of lymphoid malignancies and specifi­ cally chronic lymphocytic leukemia (CLL), are reviewed here. * Current affiliation : University of Leicester, Leicester, England. 335 336 Dyer and Osterborg II. GENERAL CONSIDERATIONS CLL and related leukemias are ideal diseases for experimental therapy with MAbs. First, the disease is usually only slowly progressive, allowing sequential observations to be made in the one patient—this is of importance when comparing related reagents as shown later.

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  Drug Disposition and Pharmacokinetics

  Principles and Applications for Medicine, Toxicology and Biotechnology

  • Stephen H. Curry, Robin Whelpton(Authors)
  • 2022(Publication Date)
  • Wiley

    (Publisher)

  Drug Disposition and Pharmacokinetics: Principles and Applications for Medicine, Toxicology and Biotechnology, Second Edition. Stephen H. Curry and Robin Whelpton. © 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd. 8.1 Introduction Monoclonal antibodies (mAbs) were mentioned briefly in Chapter 7. Their recently gained prominent position in the therapeutic armamentarium now earns them a separate chapter. The first mAbs were intro- duced successfully into medicine in the late 1990s. Some of the earliest discoveries have disappeared, but two early examples, adalimumab and trastuzumab, have revolutionized their fields of medicine and have been around long enough for patent expiry issues to arise. These two drugs are given greater emphasis later in this chapter. Monoclonal antibodies now comprise about 20% of the new drugs approved each year, reflecting a revolution in medicinal chemistry strategy. The majority of therapeutic mAbs are for oncological and immunological/infectious diseases, but rapid expansion into other disease areas is occur- ring (Recio et al., 2017; Ryman & Meibohm 2017; Castelli et al., 2019; Datta-Mannan, 2019; Grilo & Mantalaris, 2019). These compounds are distinct from the more traditional small molecule drugs by virtue of their chemistry, molecular weight (~150 kDa), polarity, methods of production, long half-life values, and mostly extracellular sites of action and from the drugs in Chapter 7 by being exclusively proteins. Their existence was made pos- sible by the development of recombinant technology, and by the other techniques of modern proteomics that ensued, as well as the realization that there were possibilities of unique drug/target interactions specific to what came to be known as ‘biologics’ (sometimes ‘disease modulators’) when compared with more traditional medicaments.

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  Monoclonal Antibody and Immunosensor Technology

  The production and application of rodent and human monoclonal antibodies

  • A.M. Campbell(Author)
  • 1991(Publication Date)
  • Elsevier Science

    (Publisher)

  The slight irony for the Mab technologist is that high-affinity Mabs may well offer inexpensive and specific therapy but they have been somewhat abused by the haste of many sectors of the biotechnology industry to achieve a marketable reagent before their competitors and, in consequence, offering inferior reagents to the market. To a considerable extent, the scientific community at all levels re- 30 MONOCLONAL ANTIBODY AND IMMUNOSENSOR TECHNOLOGY sponded to the potential use of Mabs in the 1980s by producing new methods of increasing the yield of the already extensive range of anti- bodies to small soluble proteins such as hen eggwhite lysosyme (HEL), or keyhole limpet haemocyanin (KLH) in the mouse and, where human Mabs were involved, to tetanus toxin, justifying these as ‘model systems’. However, with the exception of bacterial toxins, relevant target an- tigens were (and are) presented on complex organisms such as viruses, bacteria and whole cells and such antigens present a much greater challenge than small soluble proteins both to the immune system and the Mab technologist seeking to produce high-affinity monospecific reagents. 1.12.2. Therapyfor bacterial infection Bacterial disease is not perceived as a major problem in the developed world where the major causes of death are malignancy or failures of the cardiovascular system, both being diseases of comparatively elder- ly people. In the developing world, bacterial infections form the main contribution to mortality, particularly infant mortality, but the devel- oping world cannot afford expensive new generation reagents such as Mabs. Development of Mab techniques for bacterial infections has largely centred on areas such as sporadic outburst of public panic in food poisoning or legionella exposure, and neutralisation of toxins (see below). Bacteria, being generally extracellular parasites, are naturally at- tacked predominantly by the antibody arm of the immune response.

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  Monoclonal Antibodies in Diagnostic Immunohistochemistry

  • Mark Wick(Author)
  • 1988(Publication Date)
  • CRC Press

    (Publisher)

  CI-IAPTER 1 Theoretical and Technical Considerations for the Use of Monoclonal Antibodies in Diagnostic Immunohistochemistry Howard M. Reisner* Mark R. Wick** University of North Carolina at Chapel Hill University of Minnesota School of Medicine Chapel Hill, North Carolina Minneapolis, Minnesota PART I THEORETICAL CONSIDERATIONS It is an unfortunate but nonetheless realistic observation that the closest the average histopathologist comes to immunologic reagent production is opening the package, throwing away the insert (perhaps after reading it), and possibly rehydrating a lyophilized powder. Ultimately, however, the value of any im-munohistologically based diagnosis rests on the quality of the primary antibody reagent probe. No amount of diagnostic perspicacity or sophisticated immuno-histochemical technique can repair an irrevocably flawed, or just plain incor-rect, tool. Perhaps conditioned by an excess of marketing hype, there is a tendency for the working histopathologist to accept the cachet of monoclonal antibody (MoAb) as a guarantee of specificity and a certification of acceptable (if not exceptional) quality. Neophyte users quickly learn to adopt an appropriately skeptical attitude toward the MoAb reagents they depend on. As detailed in the second section of this chapter, this skeptical attitude is most practically manifest by a scrupulous regard for controls and in-house evaluation of new reagents. This may be sufficient to implement the use of *Part I by Howard M. Reisner. **Part II by Mark R. Wick. 2 Reisner and Wick MoAb in the histopathology laboratory. One hopes, however, that an under-standing of MoAb production combined with an appreciation of the intrinsic benefits, as well as potential liabilities, of MoAb would provide an intellectual framework useful in solving the unexpected problem or dealing with the exceptional case.

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