Interferon in the treatment of chronic hepatitis C: a drug caught between past and future

Vezali, Elena; Aghemo, Alessio; Colombo, Massimo

doi:10.1517/14712598.2011.552906

Cited by 16 publications

(13 citation statements)

References 86 publications

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“…Taking interferon as an example: PEGylation of IFNα-2 using either a 40 kDa branched PEG in the case of PEGasys ® (PEG-IFNα-2a, Roche, Switzerand) or a 12 kDa linear PEG in the case of PEG-Intron ® (PEG-IFNα-2b, Schering/Plough, USA) extends the [45]. Efficacy can be measured empirically by reduction of the sustained viral load [47][48][49][50] and prolonging the half-life helped to ensure there was a therapeutic dose present between each time the PEG-IFN was administered. Patient compliance with this therapy is greatly increased compared with that with non-PEGylated IFNα.…”

Section: Reduced Renal Clearancementioning

confidence: 99%

Pegylation and Its Impact on the Design of New Protein-Based Medicines

Ginn¹,

Khalili²,

Lever³

et al. 2014

Future Med. Chem.

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PEGylation is the covalent conjugation of PEG to therapeutic molecules. Protein PEGylation is a clinically proven approach for extending the circulation half-life and reducing the immunogenicity of protein therapeutics. Most clinically used PEGylated proteins are heterogeneous mixtures of PEG positional isomers conjugated to different residues on the protein main chain. Current research is focused to reduce product heterogeneity and to preserve bioactivity. Recent advances and possible future directions in PEGylation are described in this review. So far protein PEGylation has yielded more than 10 marketed products and in view of the lack of equally successful alternatives to extend the circulation half-life of proteins, PEGylation will still play a major role in drug delivery for many years to come.

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Section: Reduced Renal Clearancementioning

confidence: 99%

Pegylation and Its Impact on the Design of New Protein-Based Medicines

Ginn¹,

Khalili²,

Lever³

et al. 2014

Future Med. Chem.

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“…Several studies have demonstrated the suppressive effect of IFN-α in the development of HCC in patients with chronic hepatitis [45][46][47][48]. Thus IFN-α therapy for hepatitis B (HBV) and C (HCV) viral infections suppresses carcinogenesis and improves liver function [49][50][51][52]. Moreover, IFN-α therapy eliminates HCV mRNA, and reduces the development of HCC in patients with normalized transaminase levels [53].…”

Section: Ifns In Clinical Oncologymentioning

confidence: 99%

IFN-λ Cancer Immunotherapy: New Kid on the Block

et al. 2016

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Interferon-lambda (IFN-λ) is a new IFN type, related to IFN-α, that is commonly used in the clinic. However, significant side effects accompanying IFN-α treatment limit enthusiasm for IFN-α. In this review, we discuss the current landscape of IFN-α use in oncology and describe the biologic characteristics of IFN-λ. IFN-λ offers unique advantages, including a more tumor cell selective targeting, lower off-target binding and an ability to generate both innate and adaptive immune responses. IFN-λ has also demonstrated therapeutic benefit in murine cancer models. IFN-λ may be used in clinic as a single agent or in combination with other immunotherapy agents, such as immune checkpoint inhibitors. Further clinical trials will be needed to fully elucidate the potential of this novel agent in oncology.

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“…Often the two clinically used PEGylated interferon-a2 (INF-a2) products are cited as definitive examples of how a PEGylated protein has shown real benefit [104]. PEGylated INF-a2 is used to treat hepatitis C, so efficacy can be measured empirically by reduction of the sustained viral load [105][106][107][108]. Only with the use of PEG-INF-a2 and ribavirin has it become possible to cure patients of some genotypes of hepatitis C. Although now first-line treatments, there was significant loss of in vitro activity observed during preclinical development for both PEGylated INF-a2 products (Pegasys, $7%; PEG-Intron, $28%) [109].…”

Section: Protein Pegylationmentioning

confidence: 99%

Chemical and Genetic Modification

Farys¹,

Ginn²,

Badescu³

et al. 2013

Pharmaceutical Sciences Encyclopedia

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There are many natural post‐translational modifications of proteins (e.g., glycosylation, ubiquitination, acylation,and amino acid derivatization).Glycosylation is common for therapeutic proteins. Classes of proteins modified by glycosylation include monoclonal antibodies, blood factors, hematopoietic proteins, and cytokines. Excluding monoclonal antibodies, many proteins were, at least when they were first introduced to the clinic, designed to be used as a replacement protein for the corresponding endogenous protein. Maintaining control of the protein structure to be as close as possible to the structure of the endogeneous protein is therefore a key goal. In this review, we focus on (i) optimization of protein pharmacokinetics, (ii) improvement of protein properties to be used as medicines (this primarily includes reduction of immunogenic sequences and improvement of protein stability), (iii) addition of a therapeutic effect, and (iv) use of proteins as diagnostics.

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Interferon in the treatment of chronic hepatitis C: a drug caught between past and future

Abstract: Pegylated IFN-α will remain the basis of anti-HCV therapy during the next decade, since new IFN formulation are not proven to be superior or are in early stages of development and directly acting antivirals show limited antiviral activity as monotherapy.

Cited by 16 publications

References 86 publications

Pegylation and Its Impact on the Design of New Protein-Based Medicines

Pegylation and Its Impact on the Design of New Protein-Based Medicines

IFN-λ Cancer Immunotherapy: New Kid on the Block

Chemical and Genetic Modification

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