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Antibodies, Monoclonal

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This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada. [...] The parameters that had the largest impact on the manufacturer's base case were: reducing the time horizon to two years, conducting the analysis from the societal perspective, varying the duration of alemtuzumab efficacy, and using the data for confirmation of disease progression (CDP) at 24 weeks. [...] In addition, the manufacturer's NMA did not adequately explore the potential impact of clinical heterogeneity across included studies on the estimates of treatment effect, and there was a lack of statistical analysis for inconsistency, which brings into question the reliability of the synthesized evidence. [...] The modifications made to the manufacturer-submitted model include the following: continuation of treatment effect and accrual of treatment costs was based on the same assumptions for all modelled comparators confirmation period for disability progression was modified to 24 weeks annual cost of daclizumab was updated to 27,700 the London, Ontario, data set was used for modelling natural h [...] Issues for Consideration Potential for off-label use in patients with primary-progressive MS: Ocrelizumab has been approved by the US FDA and by the Australian Therapeutic Goods Administration (TGA) for the treatment of primary-progressive and relapsing forms of MS; it is the first agent approved for the treatment of primary-progressive MS.

Antibodies, Monoclonal.

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Neoplasms. --- Antibodies, monoclonal --- Antibodies, monoclonal

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Monoclonal antibodies have appeared on the market over the past 20 years. Since then, they have been manipulated to obtain molecule more suitable for some therapeutics applications. We obtained different fragments whose properties were different form full-length antibodies. The major structural difference of such fragments is that they do not usually have the Fc portion. Thus there are differences in the pharmacokinetics and pharmacodynamics. For example, fragments enter tumors faster and more deeply. They are also eliminated more quickly. Fragments which do not contain an Fc part cannot trigger ADCC (antibody dependent cellular cytotoxicity) and CDC (complement dependent cytotoxicity). On the whole, the mode of action of fragments is similar to full-length antibodies. There are three main classes of fragments. The older one consists of Fab fragments. Some of them are currently marketed. The Fab fragments are being replaced by scFv based fragments in the clinical trials. No molecule from this class is currently being marketed. There is finally the third generation molecules (VHH, IgNARs), whose development has just begun. Non-glycosylated fragments can be produced in E. coli. It is easier and more productive than using mammalian cells, which are the ones used for full-length antibodies. There isn’t much of a difference between fragments and whole antibodies regarding the cost Les anticorps monoclonaux ont fait leur apparition sur le marché lors des 20 dernières années. Depuis lors, on les a manipulés dans le but d’obtenir des molécules plus adaptées à certaines applications thérapeutiques. On a obtenu différents fragments dont les propriétés diffèrent de celles des anticorps entiers sur certains points. La différence majeure au niveau structurel est que les fragments ne possèdent généralement pas la partie Fc. Cela implique dès lors des différences au niveau pharmacocinétique et pharmacodynamique. Par exemple, les fragments pénètrent plus rapidement et profondément les tumeurs. Ils sont également plus rapidement éliminés de l’organisme. Les fragments, ne contenant pas la partie Fc, ne peuvent pas déclencher l’ADCC (antibody dependent cellular cytotoxicity) ou la CDC (complement dependent cytotoxicity). Globalement, le mode d’action des fragments est similaire à celui des anticorps entier. Il existe trois classes principales de fragments. La plus ancienne est constituée des Fabs. Quelques-uns sont sur le marché. Ils sont de plus en plus remplacés par la deuxième classe, basée sur le scFvs, dans les essais cliniques. Aucune molécule appartenant à cette classe n’est actuellement commercialisée. E,fin, il y a les molécules de troisième génération (VHH, IgNARs, …) qui commencent à entrer en développement. Les fragments non-glycosylés peuvent etre produit chez E. coli, ce qui est plus facile et rentable que l’expression à partir de cellules mammaliennes, comme c’est souvent le cas pour les anticorps entiers. Au niveau du coût, il n’y a pas de différences marquées entre les anticorps entiers et les fragments

Antibodies, Monoclonal --- Immunoglobulin Fragments

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The bronchial hyperreactivity is a state of hypersensitivity associated with various pathologies such as asthma, obstructive airway diseases, viral infections of upper respiratory, atopy, left heart failure, or eventually in case of smoking. The main mechanisms underlying this phenomenon are the smooth muscle hypertrophy, the alteration of the epithelial barrier, and also an important inflammatory component. The CD4+ T helper lymphocytes are mostly responsible for this chronic inflammation, following the release of various pro-inflammatory TH2 cytokines (IL-5, IL-4, IL-13, IL-9,...). The polynuclear eosinophils are also responsible for the liberation of inflammatory mediators, contained in their cytoplasmic granules. Actually, many anti-inflammatory therapies, modulating the immune system are being studied and some of them are using monoclonal antibodies. Potential therapeutic targets, include among others the type T lymphocytes, various TH2 cytokines, TNFα and TH 17 ceil type. Omalizumab (Xolair®) is the only monoclonal antibody, who succeeded in obtaining a marketing authorization in the treatment of severe persistent allergic asthma IgE-dependent L’hyperréactivité bronchique est un état d’hypersensibilité des bronches associé à diverses pathologies, telles que l’asthme, les maladies respiratoires obstructives, les infections virales des voies respiratoires supérieures, l’atopie, l’insuffisance cardiaque gauche ou également en cas de tabagisme. Les principaux mécanismes à la base de ce phénomène sont l’hypertrophie des fibres musculaires lisses, l’altération de la barrière épithéliale, ainsi qu’une importante composante inflammatoire. Les lymphocytes T CD4+ helper sont principalement responsables de cette inflammation chronique suite à la libération de diverses cytokines TH2 pro-inflammatoires (IL-5, IL-4, IL-13, IL-9,...). Les polynucléaires éosinophiles sont eux aussi responsables de la libération de médiateurs inflammatoires contenus dans leurs granules cytoplasmiques. A l’heure actuelle, de nombreuses thérapies anti-inflammatoires modulant le système immunitaire sont à l’étude et une partie d’entre elles utilise des anticorps monoclonaux. Les cibles thérapeutiques potentielles comprennent entre autres les cellules lymphocytaires de type T, diverses cytokines TH2, le TNFα et les cellules de type TH17. L’omalizumab (Xolair®) est le seul anticorps monoclonal ayant réussi à obtenir une AMM dans le traitement de l’asthme allergique sévère persistant IgE-dépendant

Bronchial Hyperractivity --- Antibodies, Monoclonal