Measurement of Pre-Existing IgG and IgM Antibodies against Polyethylene Glycol in Healthy Individuals

Abstract

Polyethylene glycol (PEG) is a biocompatible polymer that is often attached to therapeutic molecules to improve bioavailability and therapeutic efficacy. Although antibodies with specificity for PEG may compromise the safety and effectiveness of PEGylated medicines, the prevalence of pre-existing anti-PEG antibodies in healthy individuals is unclear. Chimeric human anti-PEG antibody standards were created to accurately measure anti-PEG IgM and IgG antibodies by direct ELISA with confirmation by a competition assay in the plasma of 1504 healthy Han Chinese donors residing in Taiwan. Anti-PEG antibodies were detected in 44.3% of healthy donors with a high prevalence of both anti-PEG IgM (27.1%) and anti-PEG IgG (25.7%). Anti-PEG IgM and IgG antibodies were significantly more common in females as compared to males (32.0% vs 22.2% for IgM, p < 0.0001 and 28.3% vs 23.0% for IgG, p = 0.018). The prevalence of anti-PEG IgG antibodies was higher in younger (up to 60% for 20 year olds) as opposed to older (20% for >50 years) male and female donors. Anti-PEG IgG concentrations were negatively associated with donor age in both females (p = 0.0073) and males (p = 0.026). Both anti-PEG IgM and IgG strongly bound PEGylated medicines. The described assay can assist in the elucidation of the impact of anti-PEG antibodies on the safety and therapeutic efficacy of PEGylated medicines.

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

“…7a). The pre-existing anti-PEG IgG concentrations ranged from 0.3 to 237.5 μg ml −1 with a mean concentration of 5.75±16.0 μg ml −1 in 386 anti-PEG positive samples27. We selected a human serum sample containing a relatively high concentration of anti-PEG IgG (51.4 μg ml −1 ).…”

Physicochemical Properties of Magnetic Nanoparticles: Implications for Biomedical Applications In Vitro and In Vivo

“…PEG is a biocompatible synthetic polymer [19]; it is often used, alone or in combination with other building blocks, to minimize unwanted interactions of the nanoparticles with plasma proteins and macrophages. The circulation time of the PEGylated nanoparticles is determined by the molecular weight of the used PEG, the PEGylation density, and the co-polymer type [15].…”

“…Anti-PEG antibodies cause accelerated blood clearance of PEG-coated nanomedicines [11,20]. Moreover, it has been reported several times that anti-PEG antibodies are also present in treatment-naïve people [19,21]. In addition to diminishing the efficacy of the PEGylated nanoparticles, this immune reaction also confers significant side-effects or risks [19].…”

“…Moreover, it has been reported several times that anti-PEG antibodies are also present in treatment-naïve people [19,21]. In addition to diminishing the efficacy of the PEGylated nanoparticles, this immune reaction also confers significant side-effects or risks [19]. The risks and mechanisms of the side-effects have been described elsewhere [22].…”

Polypeptides with High Zwitterion Density for Safe and Effective Therapeutics

“…[5][6][7][8][9] Repeated administration of PEGylated proteins, liposomes,o rn anoparticles triggered an accelerated blood clearance phenomenon that was mediated by anti-PEG antibodies.T he reduction of vascular residence time greatly limited therapeutic efficacyi nc hronic applications. [13,14] In ar ecent clinical trial of pegnivacogin, aP EGylated RNAa ptamer,p re-existing anti-PEG antibodies caused three serious allergic reactions,o ne of which was life-threatening,leading to early termination of the trial. [10][11][12] To exacerbate the situation, ah igh prevalence of pre-existing anti-PEG antibodies has been reported in the general population.…”