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  1. Article ; Online: Regulatory T cells and transplantation tolerance: Emerging from the darkness?

    Waldmann, Herman

    European journal of immunology

    2021  Volume 51, Issue 7, Page(s) 1580–1591

    Abstract: The field of tissue transplantation has revolutionized the treatment of patients with failing organs. Its success, thus far, has depended on combinations of immunosuppressive drugs that damp host immunity, while also imposing numerous unwanted side- ... ...

    Abstract The field of tissue transplantation has revolutionized the treatment of patients with failing organs. Its success, thus far, has depended on combinations of immunosuppressive drugs that damp host immunity, while also imposing numerous unwanted side-effects. There is a longstanding recognition that better treatment outcomes, will come from replacing these drugs, fully or in part, by taking advantage of tractable physiological mechanisms of self-tolerance. The past 50 years have seen many advances in the field of self-tolerance, but perhaps, the most tractable of these has been the more recent discovery of a subset T-cells (Treg) whose role is to regulate or damp immunity. This article is intended to first provide the reader with some historical background to explain why we have been slow to identify these cells, despite numerous clues to their existence, and also to indicate how little we know about how they achieve their regulatory function in averting transplant rejection. However, as is often the case in immunology, the therapeutic needs often dictate that our advances move to translation even before detailed explanations of the science are available. The final part of the article will briefly summarize how Treg are being harnessed as agents to interface with or perhaps, replace current drug combinations.
    MeSH term(s) Animals ; Graft Rejection/immunology ; Humans ; Immune Tolerance/immunology ; Immunosuppressive Agents/immunology ; T-Lymphocytes, Regulatory/immunology ; Transplantation Tolerance/immunology
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2021-05-16
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202048795
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  2. Article ; Online: Human Monoclonal Antibodies: The Benefits of Humanization.

    Waldmann, Herman

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1904, Page(s) 1–10

    Abstract: The major reasons for developing human monoclonal antibodies were to be able to efficiently manipulate their effector functions while avoiding immunogenicity seen with rodent antibodies. Those effector functions involve interactions with the complement ... ...

    Abstract The major reasons for developing human monoclonal antibodies were to be able to efficiently manipulate their effector functions while avoiding immunogenicity seen with rodent antibodies. Those effector functions involve interactions with the complement system and naturally occurring Fc receptors on diverse blood white cells. Antibody immunogenicity results from the degree to which the host immune system can recognize and react to these therapeutic agents. Thus far, there is still no generally applicable technology guaranteed to render therapeutic antibodies antigenically silent. This is not to say that the task is impossible, but rather that we need to train the immune system to help us. This can be achieved if we take advantage of natural mechanisms by which an individual can be rendered tolerant of "foreign" antigens, and as a corollary minimize the potential immunogenicity of any contaminating protein aggregates, or "aggregates" arising from antibodies complexing with their antigen. I here summarize our efforts to engineer antibodies to harness optimal effector functions, while also minimizing their immunogenicity. Potential avenues to achieve the latte are predicted from classical work showing that monomeric "foreign" immunoglobulins are good tolerogens, while aggregates of immunoglobulins ate intrinsically immunogenic. Consequently, I argue that one solution to the immunogenicity problem lies in ensuring a temporal quantitative advantage of tolerogenic non-cell-bound monomer over the cell-binding immunogenic form.
    MeSH term(s) Animals ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/genetics ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibody Affinity/immunology ; Antigens/immunology ; Genetic Engineering ; Humans ; Immune System/cytology ; Immune System/immunology ; Immune System/metabolism ; Immunoglobulin G/immunology ; Mutagenesis ; Receptors, Fc/metabolism
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antigens ; Immunoglobulin G ; Receptors, Fc
    Language English
    Publishing date 2018-12-11
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-8958-4_1
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  3. Book: Monoclonal antibody therapy

    Waldmann, Herman

    2 tab

    (Progress in allergy ; 45)

    1988  

    Author's details vol. ed. Herman Waldmann
    Series title Progress in allergy ; 45
    Collection
    Keywords Antibodies, Monoclonal / therapeutic use ; Monoklonaler Antikörper ; Therapie
    Subject Medizinische Behandlung ; Behandlung ; Krankenbehandlung
    Language English
    Size VIII, 173 S. : graph. Darst.
    Publisher Karger
    Publishing place Basel u.a.
    Publishing country Switzerland
    Document type Book
    HBZ-ID HT003229720
    ISBN 3-8055-4803-6 ; 978-3-8055-4803-8
    Database Catalogue ZB MED Medicine, Health

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  4. Article ; Online: Mechanisms of immunological tolerance.

    Waldmann, Herman

    Clinical biochemistry

    2016  Volume 49, Issue 4-5, Page(s) 324–328

    Abstract: There is increasing interest in establishing diagnostic markers of immunological tolerance applicable to efforts to minimize drug immunosuppression in transplantation and chronic immunological diseases. It is hoped that an understanding of the diverse ... ...

    Abstract There is increasing interest in establishing diagnostic markers of immunological tolerance applicable to efforts to minimize drug immunosuppression in transplantation and chronic immunological diseases. It is hoped that an understanding of the diverse mechanisms that can contribute to tolerance will guide efforts to establish diagnostic tolerance biomarkers. Not only would these be valuable for management of autoimmune diseases, transplants and allergies, but they might also guide efforts to override tolerance processes in cancer and vaccine development. Where tolerance is generated by deletion or inactivation of antigen reactive lymphocytes, it is unlikely that any long-term-valid blood biomarkers might be found. Where tolerance is mediated by active regulatory mechanisms, indicators that can be usefully measured may emerge, but these would likely show significant heterogeneity reflecting the diversity of active tolerance processes operating in different individuals. Given this, the most useful "kits" might be those "smart" enough to detect this diversity of tolerance players.
    MeSH term(s) Humans ; Immune Tolerance ; T-Lymphocytes, Regulatory/immunology
    Language English
    Publishing date 2016-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 390372-2
    ISSN 1873-2933 ; 0009-9120
    ISSN (online) 1873-2933
    ISSN 0009-9120
    DOI 10.1016/j.clinbiochem.2015.05.019
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  5. Article ; Online: Infectious tolerance. What are we missing?

    Waldmann, Herman / Graca, Luis

    Cellular immunology

    2020  Volume 354, Page(s) 104152

    MeSH term(s) Animals ; Humans ; Immune Tolerance ; Immunologic Deficiency Syndromes/immunology ; Immunologic Deficiency Syndromes/therapy ; Immunosuppression ; Immunotherapy/trends ; Lymphopenia/immunology ; Lymphopenia/therapy ; Mice ; T-Lymphocytes, Regulatory/immunology
    Language English
    Publishing date 2020-06-12
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 80094-6
    ISSN 1090-2163 ; 0008-8749
    ISSN (online) 1090-2163
    ISSN 0008-8749
    DOI 10.1016/j.cellimm.2020.104152
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  6. Book: Limiting dilution analysis of cells in the immune system

    Lefkovits, Ivan / Waldmann, Herman

    1999  

    Title variant Limiting dilution analysis software ; LDA software
    Keywords B-Lymphocytes / chemistry ; Indicator Dilution Techniques ; B-Lymphocytes / immunology ; T-Lymphocytes / chemistry ; T-Lymphocytes / immunology ; Immunity, Cellular
    Language English
    Size XVI, 285 S. : graph. Darst.
    Publisher Oxford Univ. Press
    Publishing place Oxford
    Publishing country Great Britain
    Document type Book
    Note Disketten u.d.T.: Limiting dilution analysis software. Systemvoraussetzungen: IBM Personal Computer or 100 percent compatible with an 80386 or higher processor; RAM 16 MB or more; hard disk drive with at least 4 MB free space; mouse; floppy disk drive 3.5 inch; Windows 95 or Windows NT 4.0 operating system
    Accompanying material 2 Disketten (9 cm)
    HBZ-ID HT010502479
    ISBN 0-19-850128-5 ; 978-0-19-850128-2
    Database Catalogue ZB MED Medicine, Health

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    1999 A 3346 order for loan Magazin
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  7. Article ; Online: Drug minimization in transplantation: an opinion.

    Waldmann, Herman

    Current opinion in organ transplantation

    2014  Volume 19, Issue 4, Page(s) 331–333

    MeSH term(s) Cell Transplantation ; Graft vs Host Disease/prevention & control ; Humans ; Immunosuppressive Agents/therapeutic use ; Organ Transplantation ; Periodicals as Topic
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2014-08
    Publishing country United States
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 1390429-2
    ISSN 1531-7013 ; 1087-2418
    ISSN (online) 1531-7013
    ISSN 1087-2418
    DOI 10.1097/MOT.0000000000000099
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  8. Article ; Online: Human monoclonal antibodies: the residual challenge of antibody immunogenicity.

    Waldmann, Herman

    Methods in molecular biology (Clifton, N.J.)

    2014  Volume 1060, Page(s) 1–8

    Abstract: One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short ... ...

    Abstract One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short article, I draw attention to classical work which shows that monomeric immunoglobulins are intrinsically tolerogenic if they can be prevented from creating aggregates or immune complexes. Based on these classical studies two approaches for active tolerization to therapeutic antibodies are described.
    MeSH term(s) Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Humans ; Immune Tolerance/immunology
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized
    Language English
    Publishing date 2014-05-02
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-62703-586-6_1
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  9. Article ; Online: Tolerance: an overview and perspectives.

    Waldmann, Herman

    Nature reviews. Nephrology

    2010  Volume 6, Issue 10, Page(s) 569–576

    Abstract: Self tolerance is dependent on mechanisms that operate on T cells and B cells from the earliest stages, that is, from when they first express anti-self-receptors in the primary lymphoid organs of the thymus and bone marrow, all the way through to when ... ...

    Abstract Self tolerance is dependent on mechanisms that operate on T cells and B cells from the earliest stages, that is, from when they first express anti-self-receptors in the primary lymphoid organs of the thymus and bone marrow, all the way through to when they engage with self antigens in the peripheral immune system and within tissues themselves. This continuum of checkpoints and fail-safes ensures that the risk of developing harmful autoimmune diseases remains very small. Certain tissues have a degree of privilege that allows them to mute the immune response against them by mechanisms that are also well represented in cancers. An understanding of the underlying mechanisms of self tolerance is hoped to spawn a new range of therapeutics designed to both reprogram the immune system to avoid long-term intense immunosuppression, and to override the immune system to achieve more effective immunity against cancers and persistent viral infections.
    MeSH term(s) Humans ; Immunotherapy ; Self Tolerance/immunology ; T-Lymphocytes, Regulatory/immunology
    Language English
    Publishing date 2010-08-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2490366-8
    ISSN 1759-507X ; 1759-5061
    ISSN (online) 1759-507X
    ISSN 1759-5061
    DOI 10.1038/nrneph.2010.108
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  10. Article: Reprogramming the immune system.

    Waldmann, Herman

    Clinical transplants

    2009  , Page(s) 351–362

    MeSH term(s) Allergy and Immunology/history ; Biomedical Research/history ; England ; History, 20th Century ; History, 21st Century ; Humans ; Transplantation/history ; Transplantation Immunology
    Language English
    Publishing date 2009-08-25
    Publishing country United States
    Document type Historical Article ; Journal Article ; Portrait
    ZDB-ID 607631-2
    ISSN 0890-9016
    ISSN 0890-9016
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