Immunogenicity of Polyethylene glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

Nicola d’Avanzo; Christian Celia; Antonella Barone; Maria Carafa; Luisa Di Marzio; Hélder A. Santos; Massimo Fresta

doi:10.1002/adtp.201900170

Immunogenicity of Polyethylene glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

Nicola d’Avanzo, Christian Celia, Antonella Barone, Maria Carafa, Luisa Di Marzio, Hélder A. Santos^*, Massimo Fresta^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

64 Citations (Scopus)

Abstract

PEGylation technique is currently considered the gold standard approach to provide a long and safe circulation of drugs. Although this is the accepted dogma, various clinical reports and animal studies show the occurrence of immunogenic responses against polyethylene glycol (PEG) after systemic injection. These side effects, associated with complement activation and/or anti‐PEG antibody production, result in hypersensitivity reactions and lack of therapeutic efficacy of the drug during clinical protocols. Furthermore, different healthy patients show the presence of anti‐PEG antibodies in their blood stream, even though they have not received PEGylated drugs. The aim of this review is to discuss the main mechanisms based on PEG immunogenicity and its clinical implications and report the most promising approaches to reduce these unexpected side effects.

Original language	English
Article number	1900170
Number of pages	18
Journal	Advanced Therapeutics
Volume	3
Issue number	3
DOIs	https://doi.org/10.1002/adtp.201900170
Publication status	Published - Mar-2020
Externally published	Yes

Keywords

317 Pharmacy
Anti-PEG antibodies
complement activation
hypersensitivity reactions
immunogenicity
ACCELERATED BLOOD CLEARANCE
ANTI-PEG IGM
PEGYLATED LIPOSOMAL DOXORUBICIN
ACUTE LYMPHOBLASTIC-LEUKEMIA
ACTIVATION-RELATED PSEUDOALLERGY
MEDIATED COMPLEMENT ACTIVATION
LONG-CIRCULATING LIPOSOMES
CHRONIC KIDNEY-DISEASE
SPLENIC MARGINAL ZONE
REPEATED INJECTIONS

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Immunogenicity of Polyethylene Glycol Based Nanomedicines_ Mechanisms, Clinical Implications and Systematic Approach
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title = "Immunogenicity of Polyethylene glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach",

abstract = "PEGylation technique is currently considered the gold standard approach to provide a long and safe circulation of drugs. Although this is the accepted dogma, various clinical reports and animal studies show the occurrence of immunogenic responses against polyethylene glycol (PEG) after systemic injection. These side effects, associated with complement activation and/or anti‐PEG antibody production, result in hypersensitivity reactions and lack of therapeutic efficacy of the drug during clinical protocols. Furthermore, different healthy patients show the presence of anti‐PEG antibodies in their blood stream, even though they have not received PEGylated drugs. The aim of this review is to discuss the main mechanisms based on PEG immunogenicity and its clinical implications and report the most promising approaches to reduce these unexpected side effects.",

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author = "Nicola d{\textquoteright}Avanzo and Christian Celia and Antonella Barone and Maria Carafa and {Di Marzio}, Luisa and Santos, {H{\'e}lder A.} and Massimo Fresta",

note = "M1 - 1900170",

year = "2020",

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doi = "10.1002/adtp.201900170",

language = "English",

volume = "3",

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T1 - Immunogenicity of Polyethylene glycol Based Nanomedicines

T2 - Mechanisms, Clinical Implications and Systematic Approach

AU - d’Avanzo, Nicola

AU - Celia, Christian

AU - Barone, Antonella

AU - Carafa, Maria

AU - Di Marzio, Luisa

AU - Santos, Hélder A.

AU - Fresta, Massimo

N1 - M1 - 1900170

PY - 2020/3

Y1 - 2020/3

N2 - PEGylation technique is currently considered the gold standard approach to provide a long and safe circulation of drugs. Although this is the accepted dogma, various clinical reports and animal studies show the occurrence of immunogenic responses against polyethylene glycol (PEG) after systemic injection. These side effects, associated with complement activation and/or anti‐PEG antibody production, result in hypersensitivity reactions and lack of therapeutic efficacy of the drug during clinical protocols. Furthermore, different healthy patients show the presence of anti‐PEG antibodies in their blood stream, even though they have not received PEGylated drugs. The aim of this review is to discuss the main mechanisms based on PEG immunogenicity and its clinical implications and report the most promising approaches to reduce these unexpected side effects.

AB - PEGylation technique is currently considered the gold standard approach to provide a long and safe circulation of drugs. Although this is the accepted dogma, various clinical reports and animal studies show the occurrence of immunogenic responses against polyethylene glycol (PEG) after systemic injection. These side effects, associated with complement activation and/or anti‐PEG antibody production, result in hypersensitivity reactions and lack of therapeutic efficacy of the drug during clinical protocols. Furthermore, different healthy patients show the presence of anti‐PEG antibodies in their blood stream, even though they have not received PEGylated drugs. The aim of this review is to discuss the main mechanisms based on PEG immunogenicity and its clinical implications and report the most promising approaches to reduce these unexpected side effects.

KW - 317 Pharmacy

KW - Anti-PEG antibodies

KW - complement activation

KW - hypersensitivity reactions

KW - immunogenicity

KW - ACCELERATED BLOOD CLEARANCE

KW - ANTI-PEG IGM

KW - PEGYLATED LIPOSOMAL DOXORUBICIN

KW - ACUTE LYMPHOBLASTIC-LEUKEMIA

KW - ACTIVATION-RELATED PSEUDOALLERGY

KW - MEDIATED COMPLEMENT ACTIVATION

KW - LONG-CIRCULATING LIPOSOMES

KW - CHRONIC KIDNEY-DISEASE

KW - SPLENIC MARGINAL ZONE

KW - REPEATED INJECTIONS

U2 - 10.1002/adtp.201900170

DO - 10.1002/adtp.201900170

M3 - Review article

SN - 2366-3987

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JO - Advanced Therapeutics

JF - Advanced Therapeutics

IS - 3

M1 - 1900170

ER -

Immunogenicity of Polyethylene glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

Abstract

Keywords

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