Biotechnological agents for the immunotherapy of multiple sclerosis. Principles, problems and perspectives.

Based on exciting results in animal models, a number of novel immunotherapies employing biotechnological products, rather than conventional immunosuppressants, are being developed for the treatment of multiple sclerosis. The first part of this article is a review of some fundamental concepts of immunology and offers a hypothetical scenario for the immunopathogenesis of multiple sclerosis. The second part provides a critical overview of various immunotherapies relying on modern biotechnology. For each approach, the underlying immunological principles, experimental and clinical evidence, and foreseeable problems are separately addressed. Thus, it is hoped that this article serves a dual purpose, namely to provide an update on recent advances in immunology, and to serve as a useful source of reference to immunotherapies holding promise for future treatment of multiple sclerosis.

[1]  M. Lambert,et al.  Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α , 1997, Nature.

[2]  H. Lassmann,et al.  TNF-α receptor fusion protein prevents experimental auto-immune encephalomyelitis and demyelination in Lewis rats: an overview , 1997, Journal of Neuroimmunology.

[3]  H. McFarland,et al.  Complexities in the Treatment of Autoimmune Disease , 1996, Science.

[4]  W. Heath,et al.  Induction of Autoimmune Diabetes by Oral Administration of Autoantigen , 1996, Science.

[5]  G. Kaplan,et al.  Thalidomide as an anti-TNF-α inhibitor: Implications for clinical use , 1996 .

[6]  S. Baqar,et al.  Oral cytokine administration. , 1996, Immunology today.

[7]  S. Medendorp,et al.  Interferon beta induces interleukin‐10 expression: Relevance to multiple sclerosis , 1996, Annals of neurology.

[8]  L. Wilkins Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b , 1996, Neurology.

[9]  D. Paty,et al.  Guidelines for physicians with patients on IFN beta-1b , 1996, Neurology.

[10]  D. Bourdette,et al.  Treatment of multiple sclerosis with T–cell receptor peptides: Results of a double–blind pilot trial , 1996, Nature Medicine.

[11]  Christian Confavreux,et al.  Clinical outcomes assessment in multiple sclerosis , 1996, Annals of neurology.

[12]  C. Martínez-A,et al.  Linomide prevents the lethal effect of anti-Fas antibody and reduces Fas-mediated ceramide production in mouse hepatocytes. , 1996, The Journal of clinical investigation.

[13]  C. Mackay,et al.  Chemokine receptors and T cell chemotaxis , 1996, The Journal of experimental medicine.

[14]  P. Kiener,et al.  Cytokine activation sensitizes human monocytic and endothelial cells to the cytotoxic effects of an anti-CD40 immunotoxin. , 1996, Journal of immunology.

[15]  Nitin J. Karandikar,et al.  CTLA-4: a negative regulator of autoimmune disease , 1996, The Journal of experimental medicine.

[16]  D. Topham,et al.  Vaccination with peptides from MHC class II beta chain hypervariable region causes allele-specific suppression of EAE , 1996, Journal of Neuroimmunology.

[17]  A. Thompson,et al.  New treatments for multiple sclerosis: a clinical perspective , 1996, Current opinion in neurology.

[18]  P. Linsley,et al.  Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways , 1996, Nature.

[19]  L. Nencioni,et al.  Nerve Growth Factor Is an Autocrine Survival Factor for Memory B Lymphocytes , 1996, Cell.

[20]  E. Shevach,et al.  IL-4-induced immune deviation as antigen-specific therapy for inflammatory autoimmune disease. , 1996, Immunology today.

[21]  L. Picker,et al.  Lymphocyte Homing and Homeostasis , 1996, Science.

[22]  C. Dinarello,et al.  Biologic basis for interleukin-1 in disease. , 1996, Blood.

[23]  C. Granger,et al.  Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis , 1996, Annals of neurology.

[24]  A. Vandenbark,et al.  T cell receptor peptides in treatment of autoimmune disease: Rationale and potential , 1996, Journal of neuroscience research.

[25]  J. Ihle STATs: Signal Transducers and Activators of Transcription , 1996, Cell.

[26]  B. Nag,et al.  Antigen‐Specific apoptosis in immortalized T cells by soluble MHC class II‐peptide complexes , 1996, Immunology and cell biology.

[27]  D. Golde,et al.  Soluble cytokine receptors. , 1996, Blood.

[28]  T. Friedmann Human gene therapy — an immature genie, but certainly out of the bottle , 1996, Nature Medicine.

[29]  D. Bourdette,et al.  Selective depletion of myelin–reactive T cells with the anti–OX–40 antibody ameliorates autoimmune encephalomyelitis , 1996, Nature Medicine.

[30]  P. Allen,et al.  Altered peptide ligand-induced partial T cell activation: molecular mechanisms and role in T cell biology. , 1996, Annual review of immunology.

[31]  E. Kinnunen [Beta interferon and multiple sclerosis]. , 1996, Duodecim; laaketieteellinen aikakauskirja.

[32]  E. Vitetta,et al.  Immunotoxins: an update. , 1996, Annual review of immunology.

[33]  F. Ramsdell,et al.  Fas and FasL in the homeostatic regulation of immune responses. , 1995, Immunology today.

[34]  J. Stavnezer Regulation of antibody production and class switching by TGF-beta. , 1995, Journal of immunology.

[35]  N. Hogg,et al.  Structure and function of adhesion receptors in leukocyte trafficking. , 1995, Immunology today.

[36]  G. Randolph,et al.  Chemokines and tissue injury. , 1995, The American journal of pathology.

[37]  L. Moldawer,et al.  Human tumor necrosis factor receptor (p55) and interleukin 10 gene transfer in the mouse reduces mortality to lethal endotoxemia and also attenuates local inflammatory responses , 1995, The Journal of experimental medicine.

[38]  J. Cleveland,et al.  Contenders in FasL/TNF death signaling , 1995, Cell.

[39]  A. Waisman,et al.  Major T-cell responses in multiple sclerosis. , 1995, Molecular medicine today.

[40]  T. Taniguchi Cytokine signaling through nonreceptor protein tyrosine kinases. , 1995, Science.

[41]  A. Sette,et al.  Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. , 1995, Immunity.

[42]  S. Miller,et al.  Evolution of the T‐Cell Repertoire during the Course of Experimental Immune‐Mediated Demyelinating Diseases , 1995, Immunological reviews.

[43]  S. Nagata,et al.  The Fas death factor , 1995, Science.

[44]  R. Simone,et al.  The Costimulatory Molecule B7 is Expressed on Human Microglia in Culture and in Multiple Sclerosis Acute Lesions , 1995, Journal of neuropathology and experimental neurology.

[45]  A. Fontana,et al.  The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis , 1995, Nature Medicine.

[46]  R. Kinkel,et al.  The interferons: Biological effects, mechanisms of action, and use in multiple sclerosis , 1995, Annals of neurology.

[47]  S. Endres,et al.  Enhanced tumor necrosis factor suppression and cyclic adenosine monophosphate accumulation by combination of phosphodiesterase inhibitors and prostanoids , 1995, European journal of immunology.

[48]  D. Madden The three-dimensional structure of peptide-MHC complexes. , 1995, Annual review of immunology.

[49]  K. Bendtzen,et al.  Cytokines and autoantibodies to cytokines , 1995, Stem cells.

[50]  M. Schwartz,et al.  Integrins: emerging paradigms of signal transduction. , 1995, Annual review of cell and developmental biology.

[51]  L. Jacobs,et al.  A brief history of the use of interferons as treatment of multiple sclerosis. , 1994, Archives of neurology.

[52]  K. Jellinger,et al.  Patterns of oligodendroglia pathology in multiple sclerosis. , 1994, Brain : a journal of neurology.

[53]  A. Minty,et al.  Macrophage-inactivating IL-13 suppresses experimental autoimmune encephalomyelitis in rats. , 1994, Journal of Immunology.

[54]  D. Hanley,et al.  Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains , 1994, Annals of neurology.

[55]  H. Lassmann,et al.  Experimental autoimmune panencephalitis and uveoretinitis transferred to the Lewis rat by T lymphocytes specific for the S100 beta molecule, a calcium binding protein of astroglia , 1994, The Journal of experimental medicine.

[56]  M. Gerhart,et al.  Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing , 1994, Nature.

[57]  C. Raine,et al.  Multiple sclerosis: immune system molecule expression in the central nervous system. , 1994, Journal of neuropathology and experimental neurology.

[58]  J. Goverman,et al.  T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis. , 1994, Science.

[59]  W. Paul,et al.  Lymphocyte responses and cytokines , 1994, Cell.

[60]  T. Springer Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm , 1994, Cell.

[61]  S. Romagnani Lymphokine production by human T cells in disease states. , 1994, Annual review of immunology.

[62]  R. Bast,et al.  Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. , 1994, Nature.

[63]  G. Kroemer,et al.  Linomide, a novel immunomodulator that prevents death in four models of septic shock , 1993, European journal of immunology.

[64]  Y. Cheng,et al.  Antisense oligonucleotides as therapeutic agents--is the bullet really magical? , 1993, Science.

[65]  S. Sriram,et al.  Experimental allergic encephalomyelitis: Neutralizing antibody to TGFβ1 enhances the clinical severity of the disease , 1993, Journal of Neuroimmunology.

[66]  H. Lassmann,et al.  T cells specific for the myelin oligodendrocyte glycoprotein mediate an unusual autoimmune inflammatory response in the central nervous system , 1993, European journal of immunology.

[67]  A. Lanzavecchia Identifying strategies for immune intervention. , 1993, Science.

[68]  D. Li,et al.  Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis , 1993, Neurology.

[69]  H. Weiner,et al.  Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. , 1993, Science.

[70]  K. Tracey,et al.  Tumor necrosis factor, other cytokines and disease. , 1993, Annual review of cell biology.

[71]  A. Miller,et al.  Dominance and crypticity of T cell antigenic determinants. , 1993, Annual review of immunology.

[72]  S. Snyder,et al.  Nitric oxide, a novel biologic messenger , 1992, Cell.

[73]  F. Sánchez‐Madrid,et al.  Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin , 1992, Nature.

[74]  D. Wallach,et al.  Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors , 1992, The Journal of experimental medicine.

[75]  F. Sánchez‐Madrid,et al.  Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. , 1992, Nature.

[76]  P. Vassalli,et al.  The pathophysiology of tumor necrosis factors. , 1992, Annual review of immunology.

[77]  Kenneth P. Johnson,et al.  Immunotherapy of multiple sclerosis , 1991, Journal of Neuroimmunology.

[78]  B. Weinshenker,et al.  An open trial of OKT3 in patients with multiple sclerosis , 1991, Neurology.

[79]  M. Jäättelä Biologic activities and mechanisms of action of tumor necrosis factor-alpha/cachectin. , 1991, Laboratory investigation; a journal of technical methods and pathology.

[80]  C. Brosnan,et al.  Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. , 1991, The Journal of clinical investigation.

[81]  H. Lassmann,et al.  Inflammation in the nervous system. Basic mechanisms and immunological concepts. , 1991, Revue neurologique.

[82]  P. Sperryn,et al.  Blood. , 1989, British journal of sports medicine.

[83]  B. Beutler,et al.  The biology of cachectin/TNF--a primary mediator of the host response. , 1989, Annual review of immunology.

[84]  B. Beutler,et al.  Cachectin: more than a tumor necrosis factor. , 1987, The New England journal of medicine.

[85]  W. Popik [Transforming growth factors]. , 1987, Postepy biochemii.

[86]  C. Brosnan,et al.  Prazosin treatment during the effector stage of disease suppresses experimental autoimmune encephalomyelitis in the Lewis rat. , 1986, Journal of immunology.

[87]  B. Zweiman,et al.  Isolation of myelin basic protein-reactive T-cell lines from normal human blood. , 1983, Cellular immunology.

[88]  H. Hendrickson Prevention of what? , 1983, Journal of the American Optometric Association.

[89]  H. Mcdevitt,et al.  In vivo effects of antibodies to immune response gene products: prevention of experimental allergic encephalitis. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[90]  R. Wührich [Treatment of multiple sclerosis]. , 1976, Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis.

[91]  F. Roncaroli,et al.  Neuropathology of multiple sclerosis , 2012 .

[92]  L. Spitler,et al.  EXPERIMENTAL ALLERGIC ENCEPHALITIS , 1972, The Journal of experimental medicine.

[93]  M. Woodruff,et al.  Immune Response , 1969, Nature.

[94]  Diana Crane,et al.  Science of Science , 1967, Nature.

[95]  W. L. Benedict,et al.  Multiple Sclerosis , 2007, Journal - Michigan State Medical Society.

[96]  C. Lumsden Experimental allergic encephalomyelitis. , 1949, Brain : a journal of neurology.