A new generation of high-affinity humanized PEGylated Fab� fragment anti-tumor necrosis factor-? monoclonal antibodies

Weir, Neil; Athwal, D. S.; Brown, Derek; Foulkes, Roly; Kollias, George; Nesbitt, Andrew; Popplewell, Andy; Spitali, Mari; Stephens, Sue

doi:10.1586/14750708.3.4.535

Cited by 19 publications

(20 citation statements)

References 42 publications

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“…It is a fully humanized, pegylated Fab portion of an anti-TNF-a monoclonal antibody and the only one of its kind approved for the treatment of CD [92,93]. The package insert of CZP claims that the molecule does not cross the placenta.…”

Section: Certolizumab Pegolmentioning

confidence: 99%

Safety of anti-TNF therapy in inflammatory bowel disease during pregnancy

Khan¹,

Asim²,

Lichtenstein³

2014

Expert Opin. Drug Saf.

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Section: Certolizumab Pegolmentioning

confidence: 99%

Safety of anti-TNF therapy in inflammatory bowel disease during pregnancy

Khan¹,

Asim²,

Lichtenstein³

2014

Expert Opin. Drug Saf.

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“…For example, infliximab and adalimumab are able to bind FcγR, a natural receptor for antibodies, fix complement and induce antibody‐dependent cellular cytotoxicity and complement‐dependent cytotoxicity (Arora et al ., 2009) Infliximab and adalimumab enhance also the rate of caspase‐dependent apoptosis in lamina propria lymphocytes, a mechanism mediated by tmTNF‐activated reverse signalling (ten Hove et al ., 2002). Certolizumab lacks these effector functions because it has no Fc region (Weir et al ., 2006), and does not induce apoptosis (Fossati and Nesbitt, 2005) probably because it is not able to crosslink tmTNF.…”

Section: Anti‐tnf Therapymentioning

confidence: 99%

Disruption of inflammatory signals by cytokine‐targeted therapies for inflammatory bowel diseases

Caprioli

Caruso

Sarra

et al. 2012

British J Pharmacology

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Gut inflammation occurring in patients with inflammatory bowel diseases (IBD) is associated with an excessive immune response that is directed against constituents of the normal bacterial flora and results in the production of large amounts of inflammatory cytokines. Anti-cytokine compounds, such as the neutralizing TNF antibodies, have been employed with clinical success in patients with IBD. However, nearly half of IBD patients are refractory to such treatments, response can wane with time, and anti-TNF treatment can associate with severe side effects and/or development/exacerbation of extra-intestinal immune-mediated pathologies. These observations, and the demonstration that, in IBD, the pathological process is also characterized by defects in the production and/or activity of counter-regulatory cytokines, have boosted further studies aimed at delineating novel strategies to combat the IBD-associated tissue-damaging immune response.

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“…In particular, the short hypervariable complementarity-determining region of the murine mAb HTNF40 was grafted into the framework of a human Ig Fab ¢ fragment [ 52 ] . Furthermore, this fragment was engineered with a single free cysteine at the hinge region, thus allowing a site specifi c thiol PEGylation at the C-terminus that preserved the recognition ability of the Fab ¢ fragment to bind and neutralize TNF a [ 53 ] . A branched PEG of 40 kDa was coupled to achieve a prolonged half-life of about 2 weeks.…”

Section: Thiol Pegylationmentioning

confidence: 99%

Protein PEGylation

Veronese

Pasut

2011

Long Acting Injections and Implants

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The covalent linking of poly(ethylene glycol) (PEG) has become the leading approach to improving the therapeutic effi cacy of proteins. This highly hydrophilic synthetic polymer possesses unique properties that allowed PEG to emerge as the best candidate for protein modifi cation. Beside the proven success of PEG conjugates already on the market, it should be noted that other derivatives are presently under advanced clinical trials. The increased half-life of the conjugates is probably the main reason for performing PEGylation. In addition, the possibility to greatly reduce the immunogenicity of a given protein is also a strong and determinant incentive. This last advantage offers the possibility to safely use, in the clinic, heterologous proteins that otherwise might trigger dramatic immunogenic responses or even anaphylactic reactions. This chapter introduces the reader to PEGylation strategies showing in detail its potential and the achievements obtained in the recent years. Furthermore, the future perspectives of the technique are also discussed.

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A new generation of high-affinity humanized PEGylated Fab� fragment anti-tumor necrosis factor-? monoclonal antibodies

Cited by 19 publications

References 42 publications

Safety of anti-TNF therapy in inflammatory bowel disease during pregnancy

Safety of anti-TNF therapy in inflammatory bowel disease during pregnancy

Disruption of inflammatory signals by cytokine‐targeted therapies for inflammatory bowel diseases

Protein PEGylation

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