The accelerated blood clearance (ABC) phenomenon: Clinical challenge and approaches to manage

Lila, Amr S. Abu; Kojima, Hiroshi; Ishida, Tatsuhiro

doi:10.1016/j.jconrel.2013.07.026

Cited by 544 publications

(298 citation statements)

References 83 publications

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“…[20–27] Ishida et al did extensive studies on PEG-liposome stimulated immune responses and summarized their findings in a recent review. [28] Although more reports regarding PEG immunogenicity came out during recent years, and monoclonal anti-PEG Abs became commercially available and have been used to develop analytical tools for PEGylated therapeutics[29–31] or drug delivery[32], studies on the existence of anti-PEG antibody and its clinical relevance are in its infancy. [33] Yang and Lai provided a summary of research relating to anti-PEG immunity.…”

Section: Introductionmentioning

confidence: 99%

Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation

Zhang

Sun

Liu

et al. 2016

Journal of Controlled Release

522

360

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The technique of attaching the polymer polyethylene glycol (PEG), or PEGylation, has brought more than ten protein drugs into market. The surface conjugation of PEG on proteins prolongs their blood circulation time and reduces immunogenicity by increasing their hydrodynamic size and masking surface epitopes. Despite this success, an emerging body of literature highlights the presence of antibodies produced by the immune system that specifically recognize and bind to PEG (anti-PEG Abs), including both pre-existing and treatment-induced Abs. More importantly, the existence of anti-PEG Abs has been correlated with loss of therapeutic efficacy and increase in adverse effects in several clinical reports examining different PEGylated therapeutics. To better understand the nature of anti-PEG immunity, we summarize a number of clinical reports and some critical animal studies regarding pre-existing and treatment-induced anti-PEG Abs. Various anti-PEG detection methods used in different studies were provided. Several protein modification technologies beyond PEGylation were also highlighted.

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Section: Introductionmentioning

confidence: 99%

Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation

Zhang

Sun

Liu

et al. 2016

Journal of Controlled Release

522

360

View full text Add to dashboard Cite

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“…However, it should be noted that antibodies against pegylated particles might arise after repeated administration. This effect, termed the accelerated blood clearance (ABC) phenomenon, involves the rapid immunological recognition and uptake of particles (Abu Lila et al, 2013a, Abu Lila et al, 2013b, Ichihara et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

Evaluation of anticancer activity of celastrol liposomes in prostate cancer cells

Wolfram

Suri

Huang

et al. 2014

Journal of Microencapsulation

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Context Celastrol, a natural compound derived from the herb Tripterygium wilfordii, is known to have anticancer activity, but is not soluble in water. Objective Formation of celastrol liposomes, to avoid the use of toxic solubilizing agents. Materials and methods Two different formulations of pegylated celastrol liposomes were fabricated. Liposomal characteristics and serum stability were determined using dynamic light scattering. Drug entrapment efficacy and drug release were measured spectrophotometrically. Cellular internalization and anticancer activity was measured in prostate cancer cells. Results Liposomal celastrol displayed efficient serum stability, cellular internalization and anticancer activity, comparable to that of the free drug reconstituted in dimethyl sulfoxide. Discussion and conclusion Liposomal celastrol can decrease the viability of prostate cancer cells, while eliminating the need for toxic solubilizing agents.

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“…For instance, development of poly(ethylene glycol) (PEG)-specific antibodies upon administration of PEG-coated liposomes in vivo has recently been observed, which raised questions towards the approved PEGylated therapeutics that are already in the market for use in humans. 4 Immunogenicity of nanomaterials not only leads to serious adverse reactions that can terminate the therapy, but also reduces the therapeutic efficiency. 5 The extent of interaction between nanoparticles and the immune system depends on their physicochemical properties (size, morphology, degradability, charge, hydrophobicity, presence of surface-decorating moieties, etc.…”

Section: Immunotoxicity Of Nanomaterialsmentioning

confidence: 99%

Data Mining as a Guide for the Construction of Cross-Linked Nanoparticles with Low Immunotoxicity via Control of Polymer Chemistry and Supramolecular Assembly

Elsabahy

Wooley

2015

Acc. Chem. Res.

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CONSPECTUS The potential immunotoxicity of nanoparticles that are currently being approved or in different phases of clinical trials or under rigorous in vitro and in vivo characterizations in several laboratories has recently raised special attention. Products with no apparent in vitro or in vivo toxicity may still trigger the various components of the immune system, unintentionally, and lead to serious adverse reactions. Cytokines are one of the useful biomarkers to predict the effect of biotherapeutics on modulating the immune system and for screening the immunotoxicity of nanoparticles, both in vitro and in vivo, and were found recently to partially predict the in vivo pharmacokinetics and biodistribution of nanomaterials. Control of polymer chemistry and supramolecular assembly provides a great opportunity for construction of biocompatible nanoparticles for biomedical clinical applications. However, the sources of data collected regarding immunotoxicities of nanomaterials are diverse and experiments are usually conducted using different assays and under specific conditions, making direct comparisons nearly impossible and, thus, tailoring properties of nanomaterials based on the available data is challenging. In this account, the effects of chemical structure, crosslinking, degradability, morphology, concentration and surface chemistry on the immunotoxicity of an expansive array of polymeric nanomaterials will be highlighted, with focus being given on assays conducted using the same in vitro and in vivo models and experimental conditions. Furthermore, numerical descriptive values have been utilized, uniquely, to stand for induction of cytokines by nanoparticles. This treatment of available data provides a simple and easy way to compare the immunotoxicity of various nanomaterials, and the values were found to correlate-well with published data. Based on the investigated polymeric systems in this study, valuable information has been collected that aids in the future design of nanomaterials for biomedical applications, which include: a) Immunotoxicity of nanomaterials is concentration- and dose-dependent; b) Synthesis of degradable nanoparticles is essential to decrease toxicity; c) Crosslinking minimizes the release of free polymeric chains and maintains high stability of nanoparticles, thereby, lowering their immunotoxicity; d) Lowering amine density for cationic polymers that are being utilized for nucleic acids delivery lowers the toxicity of nanoparticles; e) Among neutral, zwitterionic, anionic and cationic nanomaterials, neutral and cationic nanoparticles usually have the lowest and highest immunotoxicity, respectively; f) Morphology, dimension and surface chemistry have a great influence on the ability of nanomaterials to interact with the various components of the biological system and to modulate the immune system.

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The accelerated blood clearance (ABC) phenomenon: Clinical challenge and approaches to manage

Cited by 544 publications

References 83 publications

Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation

Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation

Evaluation of anticancer activity of celastrol liposomes in prostate cancer cells

Data Mining as a Guide for the Construction of Cross-Linked Nanoparticles with Low Immunotoxicity via Control of Polymer Chemistry and Supramolecular Assembly

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