Monoclonal antibodies in the therapy of multiple sclerosis

Stüve, Olaf; Goertsches, Robert; Mix, Eilhard; Zettl, Uwe K.

doi:10.1007/s00415-008-6006-x

Cited by 22 publications

(19 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mAbs are used to change the treatment strategies from non-specific to specific. The mAbs have the ability to revolutionize therapeutic concepts of the treatments of immune-mediated diseases, thus they are useful in this area (12). Looking for new therapeutic agents is still a crucial mission, because the difficulties of the production and the use of monoclonal antibodies have limited their applications (13).…”

Section: Introductionmentioning

confidence: 99%

Specific Single Chain Antibodies Against A Neuronal Growth Inhibitor Receptor, Nogo Receptor 1: Promising New Antibodies for the Immunotherapy of Multiple Sclerosis

Ehsaei¹,

Nejatollahi²,

Mohammadi³

2017

Shiraz E-Med J

View full text Add to dashboard Cite

Background: The Nogo-66 receptor (NgR1) is a myelin inhibitory neuronal receptor in Multiple Sclerosis (MS) and is a crucial key to axonal growth inhibition. The NgR1 inhibition role has been proved by monoclonal antibodies in many researches. Human single chain antibodies are composed of VH-linker-VL. They are tiny but powerful antibodies which have remarkable effects on treatments. Objectives: Producing specific single-chain antibodies of human against immune-dominant epitope of NgR1 and the evaluation of their reactivity against the epitope is the main goal of this study. Methods: An immunodominant epitope of NgR1 was designed using bioinformatics methods. The peptide was applied to select specific single chain antibodies using a phage antibody display library of scFv (single chain Fragment variable) and panning process. The selected clones were PCR (Polymerase Chain Reaction) amplified and DNA fingerprinted, to reveal the common patterns. Phage ELISA was performed to evaluate the reactivity of the selected scFvs. Results: Two specific clones with the frequencies of 55% and 45% were detached. Positive ELISA were detected with the corresponding epitope for clones, but for negative controls no positive reaction took place. The corresponding peptide-coated wells for scFv 1 and scFv 2 absorbed 0.81 and 0.62, respectively, which were significantly higher than the absorbance of the wells without any peptide, ie, 0.10 and 0.14, respectively. Conclusions: Using monoclonal antibody in the case of targeted therapy against NgR1 prevents Nogo-A, myelin associated glycoprotein, and oligodendrocyte from binding to Ngr1 and disturbs demyelination. Results demonstrated the selection of two specific scFvs against NgR1 which reacted with the antigen significantly. These specific, small human antibodies can be considered as blockings for Multiple Sclerosis to interfere with the axonal growth inhibition in NgR1-expressing neurons. Further studies should be conducted to find the effects of these antibodies in vitro and in vivo.

show abstract

Section: Introductionmentioning

confidence: 99%

Specific Single Chain Antibodies Against A Neuronal Growth Inhibitor Receptor, Nogo Receptor 1: Promising New Antibodies for the Immunotherapy of Multiple Sclerosis

Ehsaei¹,

Nejatollahi²,

Mohammadi³

2017

Shiraz E-Med J

View full text Add to dashboard Cite

show abstract

“…47 IgG 1 (and IgG 3 ) bind all FcγRs and fix complement and thus have the greatest potential for Fc-mediated effector function ( Table 3). IgG 4 and IgG 2 on the other hand do not bind or bind weakly to FcγRs and hence have little or no effector function, although IgG 2 can bind more strongly to certain allelic forms of FcγRIIA (131H and 131R) and FcγRIIIA (V158) in some individuals. IgG 2 has very poor complement fixation activity whereas IgG 4 does not fix complement (Table 3).…”

Section: Assessing Potential Immunotoxicity Concerns Of Mabs By Evalumentioning

confidence: 99%

“…Since the major indications for therapeutic monoclonal antibodies (mAbs), defined here as mAbs, fragments thereof and Fc-fusion proteins, are cancer and inflammatory/autoimmune disease, [1][2][3][4][5][6][7][8] a large proportion of the products approved for human use ( Table 1) or in clinical development are designed to directly or indirectly modulate one or more aspects of the immune system (humoral, cell-mediated and innate immunity), and therefore have the potential to induce either immune suppression or immune activation. Therapeutic mAbs, including immunomodulatory mAbs, have generally proven to be safe, and in many cases, effective pharmaceuticals.…”

Section: Introductionmentioning

confidence: 99%

Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies

Brennan

Morton

Spindeldreher

et al. 2010

mAbs

211

155

View full text Add to dashboard Cite

Abbreviations: ADA, anti-drug antibody; ADCC, antibody-dependent cellular cytotoxicity; ADME, absorption, distribution, metabolism and excretion; APC, antigen-presenting cell; AS, ankylosing spondylitis; CAPS, cropyrin-associated periodic syndromes; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; CDR, complementarity-determining region; CMV, cytomegalovirus; COPD, chronic obstructive pulmonary disease; CRA, cytokine release assay; CrD, Crohn disease; CRS, cytokine release syndrome; CTLA-4, cytotoxic T lymphocyte antigen-4; DAMPs, damage-associated molecular patterns; DC, dendritic cell; DTH, delayed-type hypersensitivity; EBV, Epstein Barr virus; EFD-PPND, embryo-fetal development and peri-/ post-natal development; EMA, European Medicines Agency; EPAR, European Public Assessment Report; EPO, erythropoietin; ESG, Expert Scientific Group; FDA, Food and Drug Administration; FIH, first-in-human; GD, gestation day; GLP, good laboratory practice; HED, human equivalent dose; HHV-8, human herpes virus-8; HLA, human leukocyte antigen; HSA, human serum albumin; HSP, heat shock protein; HTLV-1, human T cell leukemia virus-1; ICH, International Conference on Harmonization; IHC, immunohistochemistry; KLH, keyhole limpet hemocyanin; LCV, lymphocryptovirus; LFA-1, leukocyte function antigen-1; LPS, lipopolysaccharide; mAb, monoclonal antibody; MABEL, minimum anticipated biological effect level; MHC, major histocompatibility comlex; MoA, mechanism of action; MRSD, maximum recommended starting dose; MS, multiple sclerosis; NCE, new chemical entity; NHP, non-human primate; NK, natural killer; NLR, nod-like receptor; NOAEL, no observed adverse effect level; PAD, pharmacologically-active dose; PAMPs, pathogen-associated molecular patterns; PEG-MGDF, pegylated megakaryocyte growth and development factor; PD, pharmacodynamic; PHA, phytohemaglutinin; PK, pharmacokinetic; PML, progressive multifocal leukoencephalopathy; PsA, psoriatic arthritis; RA, rheumatoid arthritis; RMP, risk management plan; RO, receptor occupancy; RSV, respiratory syncytial virus; SBA, summary basis of approval; SLE, systemic lupus erythromatosus; SPC, summary of product characteristics; SRBC, sheep red blood cell; TCR, tissue cross reactivity; TDAR, T cell-dependent antibody response; TLR, toll-like receptor; TT, tetanus toxoid; UC, ulcerative colitis; VLA-4, very late antigen-4Most therapeutic monoclonal antibodies (mAbs) licensed for human use or in clinical development are indicated for treatment of patients with cancer and inflammatory/autoimmune disease and as such, are designed to directly interact with the immune system. A major hurdle for the development and early clinical investigation of many of these immunomodulatory mAbs is their inherent risk for adverse immune-mediated drug reactions in humans such as infusion reactions, cytokine storms, immunosuppression and autoimmunity. A thorough understanding of the immunopharmacology of a mAb in humans and animals is required to both anticipate the clinical risk of adverse immunotoxic...

show abstract

“…[66] It produces antibody-dependent cellular cytotoxicity with rapid and profound lymphopenia lasting for years. [67] CAMMS223 was a randomized phase II trial comparing alemtuzumab with IFN-β1a in the treatment of early RRMS.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Advances in the treatment of relapsing - Remitting multiple sclerosis

Tanasescu¹,

Ionete²,

Chou³

et al. 2014

Biomed J

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS). Pathologic hallmarks of MS lesions are inflammation, demyelination, axonal degeneration, neuronal loss, and gliosis. [1,2] MS is the most common neurological non-traumatic cause of disability in young people in the western world. MS initially presents in most patients as a relapsing-remitting condition (RRMS), but the majority of RRMS individuals develop a secondary progressive course (SPMS) later. [3] In fewer cases, the disease progresses from the beginning without superimposed relapses [primary progressive MS (PPMS)] or with rare superimposed relapses [progressive relapsing MS (PRMS)]. [4] The clinical signs in MS can occur in isolation or in combination, and can include motor and sensory deficits, partial or complete visual loss, diplopia, impaired coordination, and gait dysfunction. The diagnosis specifically integrates magnetic resonance imaging (MRI) with clinical attacks and paraclinical methods, and implies the dissemination of inflammatory activity in time and space. [5] MS treatments tackle separately the acute exacerbations and their prevention. Pharmacological management of relapses involves the use of corticosteroids, while approved long-term treatments [disease-modifying treatments (DMTs)] aim to decrease the clinical relapse rate and concomitant inflammation within the CNS.MS therapeutic landscape is changing rapidly. After several years in which first-line DMTs -glatiramer acetate (GA) and interferon β (IFNβ) -constituted the principal treatment options, a variety of new agents for MS treatment are now approved by regulatory authorities or in phase II and III clinical trials.[6] In 2010, fingolimod, the first oral agent, Special EditionThis article reviews and discusses the approved and emerging therapies for multiple sclerosis (MS). MS is a chronic and disabling immune-mediated disease of the central nervous system (CNS) that affects mainly young adults. MS imposes a huge economic burden on healthcare systems and the society. Although the last 20 years have brought a continuous expansion in therapeutic options, there are still unmet needs in MS management. Available MS drugs have varying degrees of efficacy in reducing relapse risk. The long-term term effects of these treatments are incompletely known. New therapies, along with variations of currently available treatments, may prove more effective and tolerable than the available drugs. Treatments for MS differ with respect to the mode of administration, tolerability and likelihood of treatment adherence, side effects, and risk of major toxicity. The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone)...

show abstract

Monoclonal antibodies in the therapy of multiple sclerosis

Cited by 22 publications

References 81 publications

Specific Single Chain Antibodies Against A Neuronal Growth Inhibitor Receptor, Nogo Receptor 1: Promising New Antibodies for the Immunotherapy of Multiple Sclerosis

Specific Single Chain Antibodies Against A Neuronal Growth Inhibitor Receptor, Nogo Receptor 1: Promising New Antibodies for the Immunotherapy of Multiple Sclerosis

Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies

Advances in the treatment of relapsing - Remitting multiple sclerosis

Contact Info

Product

Resources

About