About this Research Topic
Polyethylene glycols (PEGs) are nonionic polymers of ethylene oxide commercially available over a wide range of molecular weights, from 200 to 40,000 Da, and are utilized in thousands of medical and pharmaceutical products, either as active ingredients or excipients. Polyethylene glycol (PEG) modification, known as PEGylation, represents a highly successful strategy for enhancing the therapeutic properties of protein products. PEGylation increases the size of proteins, inhibits proteolysis, and reduces renal filtration, thereby improving the pharmacokinetics (half-life) of protein drugs. Currently, there are more than twenty pegylated drugs, including biosimilars, approved by the FDA, with more in various stages of development.
Despite the success in achieving improved pharmacokinetics, PEG and PEGylated drugs have been associated with a small but notable rate (reported to range from less than 0.1% to 9%) of acute allergic reactions, often occurring upon initial treatment with PEGylated drugs. While the incidence may be relatively low, allergic reactions, particularly anaphylaxis, can pose life-threatening risks. In some instances, the frequency of severe reactions has been significant enough to prompt the withdrawal of otherwise promising drugs from the market. Additionally, there has been a growing number of reports indicating immediate hypersensitivity reactions to PEG in unrelated products.
During the investigation into the root cause of allergic reactions to peginesatide following its recall, our laboratory developed a sensitive method for accurately detecting pre-existing and induced immunogenicity to the PEG component of these products. This method exhibits sufficient sensitivity to detect anti-PEG IgE, an antibody isotype mechanistically linked to acute allergic reactions, in human serum. This represents the first reliable in vitro evidence of PEG-associated type 1 hypersensitization, resolving a nearly three-decade-long enigma since the first approval of PEGylated products.
However, despite advancements, allergy to PEG and/or PEG-containing lipid nanoparticle formulations (e.g., mRNA/COVID vaccines) remains a challenge, primarily due to the lack of standardized and reliable assays for clinical assessment. To address this issue, we intend to organize a special issue, inviting experts from clinical, academic, and regulatory backgrounds to focus on the challenges of PEG allergy and immunogenicity, exchange ideas, and explore potential solutions.
The topic editors declare no conflict of interests
Despite the success in achieving improved pharmacokinetics, PEG and PEGylated drugs have been associated with a small but notable rate (reported to range from less than 0.1% to 9%) of acute allergic reactions, often occurring upon initial treatment with PEGylated drugs. While the incidence may be relatively low, allergic reactions, particularly anaphylaxis, can pose life-threatening risks. In some instances, the frequency of severe reactions has been significant enough to prompt the withdrawal of otherwise promising drugs from the market. Additionally, there has been a growing number of reports indicating immediate hypersensitivity reactions to PEG in unrelated products.
During the investigation into the root cause of allergic reactions to peginesatide following its recall, our laboratory developed a sensitive method for accurately detecting pre-existing and induced immunogenicity to the PEG component of these products. This method exhibits sufficient sensitivity to detect anti-PEG IgE, an antibody isotype mechanistically linked to acute allergic reactions, in human serum. This represents the first reliable in vitro evidence of PEG-associated type 1 hypersensitization, resolving a nearly three-decade-long enigma since the first approval of PEGylated products.
However, despite advancements, allergy to PEG and/or PEG-containing lipid nanoparticle formulations (e.g., mRNA/COVID vaccines) remains a challenge, primarily due to the lack of standardized and reliable assays for clinical assessment. To address this issue, we intend to organize a special issue, inviting experts from clinical, academic, and regulatory backgrounds to focus on the challenges of PEG allergy and immunogenicity, exchange ideas, and explore potential solutions.
The topic editors declare no conflict of interests
Keywords: PEG, Vaccines, Allergic Reactions, Immunology
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