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  1. Article ; Online: Getting specific: targeting Fc receptors in myasthenia gravis.

    Lünemann, Jan D

    Nature reviews. Neurology

    2021  Volume 17, Issue 10, Page(s) 597–598

    MeSH term(s) Autoantibodies ; Humans ; Myasthenia Gravis/drug therapy ; Receptors, Fc
    Chemical Substances Autoantibodies ; Receptors, Fc
    Language English
    Publishing date 2021-08-23
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2491514-2
    ISSN 1759-4766 ; 1759-4758
    ISSN (online) 1759-4766
    ISSN 1759-4758
    DOI 10.1038/s41582-021-00547-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6257: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 88: Show issues

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  2. Article ; Online: Autophagy pathways in autoimmune diseases.

    Keller, Christian W / Adamopoulos, Iannis E / Lünemann, Jan D

    Journal of autoimmunity

    2023  Volume 136, Page(s) 103030

    Abstract: Autophagy comprises a growing range of cellular pathways, which occupy central roles in response to energy deprivation, organelle turnover and proteostasis. Over the years, autophagy has been increasingly linked to governing several aspects of immunity, ... ...

    Abstract Autophagy comprises a growing range of cellular pathways, which occupy central roles in response to energy deprivation, organelle turnover and proteostasis. Over the years, autophagy has been increasingly linked to governing several aspects of immunity, including host defence against various pathogens, unconventional secretion of cytokines and antigen presentation. While canonical autophagy-mediated antigen processing in thymic epithelial cells supports the generation of a self-tolerant CD4
    MeSH term(s) Animals ; Autoimmune Diseases/therapy ; Autophagy ; Lupus Erythematosus, Systemic/therapy ; Arthritis, Rheumatoid ; Histocompatibility Antigens Class II/metabolism ; Autoantigens
    Chemical Substances Histocompatibility Antigens Class II ; Autoantigens
    Language English
    Publishing date 2023-03-29
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 639452-8
    ISSN 1095-9157 ; 0896-8411
    ISSN (online) 1095-9157
    ISSN 0896-8411
    DOI 10.1016/j.jaut.2023.103030
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    Zs.A 2368: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Synthetic Cell-Based Immunotherapies for Neurologic Diseases.

    von Baumgarten, Louisa / Stauss, Hans J / Lünemann, Jan D

    Neurology(R) neuroimmunology & neuroinflammation

    2023  Volume 10, Issue 5

    Abstract: The therapeutic success and widespread approval of genetically engineered T cells for a variety of hematologic malignancies spurred the development of synthetic cell-based immunotherapies for CNS lymphoma, primary brain tumors, and a growing spectrum of ... ...

    Abstract The therapeutic success and widespread approval of genetically engineered T cells for a variety of hematologic malignancies spurred the development of synthetic cell-based immunotherapies for CNS lymphoma, primary brain tumors, and a growing spectrum of nononcologic disease conditions of the nervous system. Chimeric antigen receptor effector T cells bear the potential to deplete target cells with higher efficacy, better tissue penetration, and greater depth than antibody-based cell depletion therapies. In multiple sclerosis and other autoimmune disorders, engineered T-cell therapies are being designed and currently tested in clinical trials for their safety and efficacy to eliminate pathogenic B-lineage cells. Chimeric autoantibody receptor T cells expressing a disease-relevant autoantigen as cell surface domains are designed to selectively deplete autoreactive B cells. Alternative to cell depletion, synthetic antigen-specific regulatory T cells can be engineered to locally restrain inflammation, support immune tolerance, or efficiently deliver neuroprotective factors in brain diseases in which current therapeutic options are very limited. In this article, we illustrate prospects and bottlenecks for the clinical development and implementation of engineered cellular immunotherapies in neurologic diseases.
    MeSH term(s) Humans ; Artificial Cells ; Nervous System Diseases/therapy ; Immunotherapy ; Brain Diseases ; Autoantibodies
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2767740-0
    ISSN 2332-7812 ; 2332-7812
    ISSN (online) 2332-7812
    ISSN 2332-7812
    DOI 10.1212/NXI.0000000000200139
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Antibody-mediated cell depletion therapies in multiple sclerosis.

    Mariottini, Alice / Muraro, Paolo A / Lünemann, Jan D

    Frontiers in immunology

    2022  Volume 13, Page(s) 953649

    Abstract: Development of disease-modifying therapies including monoclonal antibody (mAb)-based therapeutics for the treatment of multiple sclerosis (MS) has been extremely successful over the past decades. Most of the mAb-based therapies approved for MS deplete ... ...

    Abstract Development of disease-modifying therapies including monoclonal antibody (mAb)-based therapeutics for the treatment of multiple sclerosis (MS) has been extremely successful over the past decades. Most of the mAb-based therapies approved for MS deplete immune cell subsets and act through activation of cellular Fc-gamma receptors expressed by cytotoxic lymphocytes and phagocytes, resulting in antibody-dependent cellular cytotoxicity or by initiation of complement-mediated cytotoxicity. The therapeutic goal is to eliminate pathogenic immune cell components and to potentially foster the reconstitution of a new and healthy immune system. Ab-mediated immune cell depletion therapies include the CD52-targeting mAb alemtuzumab, CD20-specific therapeutics, and new Ab-based treatments which are currently being developed and tested in clinical trials. Here, we review recent developments in effector mechanisms and clinical applications of Ab-based cell depletion therapies, compare their immunological and clinical effects with the prototypic immune reconstitution treatment strategy, autologous hematopoietic stem cell transplantation, and discuss their potential to restore immunological tolerance and to achieve durable remission in people with MS.
    MeSH term(s) Alemtuzumab/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antigens, CD20 ; Humans ; Immunotherapy/methods ; Multiple Sclerosis
    Chemical Substances Antibodies, Monoclonal ; Antigens, CD20 ; Alemtuzumab (3A189DH42V)
    Language English
    Publishing date 2022-09-12
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.953649
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Targeting sialylation to treat central nervous system diseases.

    Lünemann, Jan D / von Gunten, Stephan / Neumann, Harald

    Trends in pharmacological sciences

    2021  Volume 42, Issue 12, Page(s) 998–1008

    Abstract: Sialic acid-binding immunoglobulin-type lectins (SIGLECs) are membrane receptors that are preferentially expressed on immune cells and recognize sialylated proteins, lipids, and RNA. Sialic acids and signaling through SIGLECs are increasingly recognized ... ...

    Abstract Sialic acid-binding immunoglobulin-type lectins (SIGLECs) are membrane receptors that are preferentially expressed on immune cells and recognize sialylated proteins, lipids, and RNA. Sialic acids and signaling through SIGLECs are increasingly recognized for their essential roles in immune system homeostasis as well as nervous system development, plasticity, and repair. Dysregulated sialylation and SIGLEC dysfunctions contribute to several chronic diseases of the central nervous system (CNS) in which current therapeutic options are very limited. While only a few therapies targeting SIGLECs are currently being tested in clinical trials, the area emerged as one of the most dynamic and active fields in glycobiology and drug development. This review highlights recent insights into sialic acid and SIGLEC function in CNS pathologies and illustrates opportunities and challenges for the development of sialic acid-based and SIGLEC-targeted therapies for neurological diseases.
    MeSH term(s) Central Nervous System/metabolism ; Central Nervous System Diseases/drug therapy ; Humans ; N-Acetylneuraminic Acid/metabolism ; Sialic Acid Binding Immunoglobulin-like Lectins/metabolism
    Chemical Substances Sialic Acid Binding Immunoglobulin-like Lectins ; N-Acetylneuraminic Acid (GZP2782OP0)
    Language English
    Publishing date 2021-10-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 282846-7
    ISSN 1873-3735 ; 0165-6147
    ISSN (online) 1873-3735
    ISSN 0165-6147
    DOI 10.1016/j.tips.2021.09.002
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    Zs.A 1513: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 6: Show issues

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  6. Article ; Online: Noncanonical autophagy in dendritic cells triggers CNS autoimmunity.

    Keller, Christian W / Lünemann, Jan D

    Autophagy

    2018  Volume 14, Issue 3, Page(s) 560–561

    Abstract: Reactivation and expansion of myelin-reactive ... ...

    Abstract Reactivation and expansion of myelin-reactive CD4
    MeSH term(s) Animals ; Antigen Presentation/immunology ; Antigens/immunology ; Autoimmunity/immunology ; Autophagy/immunology ; CD4-Positive T-Lymphocytes/immunology ; Central Nervous System/immunology ; Dendritic Cells/immunology ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Mice ; Phagocytosis/immunology
    Chemical Substances Antigens
    Language English
    Publishing date 2018-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2018.1427397
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6741: Show issues Location:
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  7. Article ; Online: Autophagy Pathways in CNS Myeloid Cell Immune Functions.

    Keller, Christian W / Münz, Christian / Lünemann, Jan D

    Trends in neurosciences

    2020  Volume 43, Issue 12, Page(s) 1024–1033

    Abstract: The CNS accommodates a diverse myeloid immune cell compartment that maintains CNS homeostasis in the steady state while contributing to tissue injury during infectious, autoimmune, and neurodegenerative disease conditions. Autophagy and autophagy ... ...

    Abstract The CNS accommodates a diverse myeloid immune cell compartment that maintains CNS homeostasis in the steady state while contributing to tissue injury during infectious, autoimmune, and neurodegenerative disease conditions. Autophagy and autophagy proteins play fundamental roles in myeloid cell-related immune functions. Many of these processes do not necessarily involve the canonical formation of a double-membrane structure known as the 'autophagosome' and reflect noncanonical functions of the autophagy machinery. Here, we illustrate recent insights, concepts, and outstanding questions regarding how autophagy pathways in myeloid cells contribute to brain health and disease.
    MeSH term(s) Autophagy ; Brain ; Humans ; Immunity ; Myeloid Cells ; Neurodegenerative Diseases
    Language English
    Publishing date 2020-09-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 282488-7
    ISSN 1878-108X ; 0378-5912 ; 0166-2236
    ISSN (online) 1878-108X
    ISSN 0378-5912 ; 0166-2236
    DOI 10.1016/j.tins.2020.09.003
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    Zs.A 1442: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 53: Show issues

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  8. Article ; Online: Fc-Receptor Targeted Therapies for the Treatment of

    Keller, Christian W / Pawlitzki, Marc / Wiendl, Heinz / Lünemann, Jan D

    International journal of molecular sciences

    2021  Volume 22, Issue 11

    Abstract: Myasthenia ... ...

    Abstract Myasthenia gravis
    MeSH term(s) Animals ; Autoantibodies/immunology ; Histocompatibility Antigens Class I ; Humans ; Immunoglobulin Fc Fragments/pharmacology ; Immunoglobulin Fc Fragments/therapeutic use ; Immunoglobulin G/immunology ; Immunologic Factors/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Immunotherapy ; Myasthenia Gravis/drug therapy ; Myasthenia Gravis/physiopathology ; Precision Medicine ; Receptors, Cholinergic/immunology ; Receptors, Fc/chemistry ; Receptors, Fc/drug effects
    Chemical Substances Autoantibodies ; Histocompatibility Antigens Class I ; Immunoglobulin Fc Fragments ; Immunoglobulin G ; Immunologic Factors ; Immunosuppressive Agents ; Receptors, Cholinergic ; Receptors, Fc ; Fc receptor, neonatal (TW3XAW0RCY)
    Language English
    Publishing date 2021-05-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22115755
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  9. Article ; Online: Next-generation antibody-based therapies in neurology.

    Ruck, Tobias / Nimmerjahn, Falk / Wiendl, Heinz / Lünemann, Jan D

    Brain : a journal of neurology

    2021  Volume 145, Issue 4, Page(s) 1229–1241

    Abstract: Antibody-based therapeutics are now standard in the treatment of neuroinflammatory diseases, and the spectrum of neurological diseases targeted by those approaches continues to grow. The efficacy of antibody-based drug platforms is largely determined by ... ...

    Abstract Antibody-based therapeutics are now standard in the treatment of neuroinflammatory diseases, and the spectrum of neurological diseases targeted by those approaches continues to grow. The efficacy of antibody-based drug platforms is largely determined by the specificity-conferring antigen-binding fragment (Fab) and the crystallizable fragment (Fc) driving antibody function. The latter provides specific instructions to the immune system by interacting with cellular Fc receptors and complement components. Extensive engineering efforts have enabled tuning of Fc functions to modulate effector functions and to prolong or reduce antibody serum half-lives. Technologies that improve bioavailability of antibody-based treatment platforms within the CNS parenchyma are being developed and could invigorate drug discovery for a number of brain diseases for which current therapeutic options are limited. These powerful approaches are currently being tested in clinical trials or have been successfully translated into the clinic. Here, we review recent developments in the design and implementation of antibody-based treatment modalities in neurological diseases.
    MeSH term(s) Antibodies/therapeutic use ; Humans ; Immunoglobulin Fab Fragments ; Immunologic Factors ; Neurology ; Receptors, Fc
    Chemical Substances Antibodies ; Immunoglobulin Fab Fragments ; Immunologic Factors ; Receptors, Fc
    Language English
    Publishing date 2021-12-16
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80072-7
    ISSN 1460-2156 ; 0006-8950
    ISSN (online) 1460-2156
    ISSN 0006-8950
    DOI 10.1093/brain/awab465
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    Ui II Zs.26: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  10. Article ; Online: Neonatal Fc Receptor-Targeted Therapies in Neurology.

    Nelke, Christopher / Spatola, Marianna / Schroeter, Christina B / Wiendl, Heinz / Lünemann, Jan D

    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

    2022  Volume 19, Issue 3, Page(s) 729–740

    Abstract: Autoantibodies are increasingly recognized for their pathogenic potential in a growing number of neurological diseases. While myasthenia gravis represents the prototypic antibody (Ab)-mediated neurological disease, many more disorders characterized by ... ...

    Abstract Autoantibodies are increasingly recognized for their pathogenic potential in a growing number of neurological diseases. While myasthenia gravis represents the prototypic antibody (Ab)-mediated neurological disease, many more disorders characterized by Abs targeting neuronal or glial antigens have been identified over the past two decades. Depletion of humoral immune components including immunoglobulin G (IgG) through plasma exchange or immunoadsorption is a successful therapeutic strategy in most of these disease conditions. The neonatal Fc receptor (FcRn), primarily expressed by endothelial and myeloid cells, facilitates IgG recycling and extends the half-life of IgG molecules. FcRn blockade prevents binding of endogenous IgG to FcRn, which forces these antibodies into lysosomal degradation, leading to IgG depletion. Enhancing the degradation of endogenous IgG by FcRn-targeted therapies proved to be a powerful therapeutic approach in patients with generalized MG and is currently being tested in clinical trials for several other neurological diseases including autoimmune encephalopathies, neuromyelitis optica spectrum disorders, and inflammatory neuropathies. This review illustrates mechanisms of FcRn-targeted therapies and appraises their potential to treat neurological diseases.
    MeSH term(s) Humans ; Immunoglobulin G ; Nervous System Diseases/drug therapy ; Neurology ; Receptors, Fc/antagonists & inhibitors ; Receptors, Fc/chemistry
    Chemical Substances Immunoglobulin G ; Receptors, Fc ; Fc receptor, neonatal (TW3XAW0RCY)
    Language English
    Publishing date 2022-01-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2316693-9
    ISSN 1878-7479 ; 1933-7213
    ISSN (online) 1878-7479
    ISSN 1933-7213
    DOI 10.1007/s13311-021-01175-7
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    Zs.A 6156: Show issues Location:
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