Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists

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

Standard

Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists. / Stavnsbjerg, Camilla; Christensen, Esben; Münter, Rasmus; Henriksen, Jonas R.; Fach, Matthias; Parhamifar, Ladan; Christensen, Camilla; Kjaer, Andreas; Hansen, Anders E.; Andresen, Thomas L.

In: Journal of Controlled Release, Vol. 342, 2022, p. 337-344.

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

Harvard

Stavnsbjerg, C, Christensen, E, Münter, R, Henriksen, JR, Fach, M, Parhamifar, L, Christensen, C, Kjaer, A, Hansen, AE & Andresen, TL 2022, 'Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists', Journal of Controlled Release, vol. 342, pp. 337-344. https://doi.org/10.1016/j.jconrel.2021.12.033

APA

Stavnsbjerg, C., Christensen, E., Münter, R., Henriksen, J. R., Fach, M., Parhamifar, L., Christensen, C., Kjaer, A., Hansen, A. E., & Andresen, T. L. (2022). Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists. Journal of Controlled Release, 342, 337-344. https://doi.org/10.1016/j.jconrel.2021.12.033

Vancouver

Stavnsbjerg C, Christensen E, Münter R, Henriksen JR, Fach M, Parhamifar L et al. Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists. Journal of Controlled Release. 2022;342:337-344. https://doi.org/10.1016/j.jconrel.2021.12.033

Author

Stavnsbjerg, Camilla ; Christensen, Esben ; Münter, Rasmus ; Henriksen, Jonas R. ; Fach, Matthias ; Parhamifar, Ladan ; Christensen, Camilla ; Kjaer, Andreas ; Hansen, Anders E. ; Andresen, Thomas L. / Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists. In: Journal of Controlled Release. 2022 ; Vol. 342. pp. 337-344.

Bibtex

@article{409ec7bdda364a35a636c862b6d6a766,
title = "Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists",
abstract = "Systemic administration of toll-like receptor (TLR) agonists have demonstrated impressive preclinical results as an anti-cancer therapy due to their potent innate immune-stimulatory properties. The clinical advancement has, however, been hindered by severe adverse effects due to systemic activation of the immune system. Liposomal drug delivery systems may modify biodistribution, cellular uptake, and extend blood circulation, and thus, potentially enable systemic administration of TLR agonists at therapeutic doses. In this study, we investigated potential barriers for the administration of TLR agonists formulated in polyethylene glycosylated (PEGylated) liposomes with regards to liposome formulation, TLR agonist, administration route, administration schedule, biodistribution, blood clearance, and anti-PEG antibodies. We found that administration of TLR agonists formulated in PEGylated liposomes led to high anti-PEG antibody titers, which upon multiple intravenous administrations, resulted in accelerated blood clearance and acute hypersensitivity reactions. The latter was found to be associated with anti-PEG IgG antibody and not anti-PEG IgM antibody opsonization. This study highlights the need to carefully design and evaluate nanoparticle delivery systems for immunotherapy as anti-nanoparticle immune responses may challenge the therapeutic application.",
keywords = "Anti-PEG antibodies, Hypersensitivity, Liposomes, PEG, PEGylated liposomes, Systemic dosing, TLRs, Toll-like receptor agonists",
author = "Camilla Stavnsbjerg and Esben Christensen and Rasmus M{\"u}nter and Henriksen, {Jonas R.} and Matthias Fach and Ladan Parhamifar and Camilla Christensen and Andreas Kjaer and Hansen, {Anders E.} and Andresen, {Thomas L.}",
note = "Publisher Copyright: {\textcopyright} 2021",
year = "2022",
doi = "10.1016/j.jconrel.2021.12.033",
language = "English",
volume = "342",
pages = "337--344",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists

AU - Stavnsbjerg, Camilla

AU - Christensen, Esben

AU - Münter, Rasmus

AU - Henriksen, Jonas R.

AU - Fach, Matthias

AU - Parhamifar, Ladan

AU - Christensen, Camilla

AU - Kjaer, Andreas

AU - Hansen, Anders E.

AU - Andresen, Thomas L.

N1 - Publisher Copyright: © 2021

PY - 2022

Y1 - 2022

N2 - Systemic administration of toll-like receptor (TLR) agonists have demonstrated impressive preclinical results as an anti-cancer therapy due to their potent innate immune-stimulatory properties. The clinical advancement has, however, been hindered by severe adverse effects due to systemic activation of the immune system. Liposomal drug delivery systems may modify biodistribution, cellular uptake, and extend blood circulation, and thus, potentially enable systemic administration of TLR agonists at therapeutic doses. In this study, we investigated potential barriers for the administration of TLR agonists formulated in polyethylene glycosylated (PEGylated) liposomes with regards to liposome formulation, TLR agonist, administration route, administration schedule, biodistribution, blood clearance, and anti-PEG antibodies. We found that administration of TLR agonists formulated in PEGylated liposomes led to high anti-PEG antibody titers, which upon multiple intravenous administrations, resulted in accelerated blood clearance and acute hypersensitivity reactions. The latter was found to be associated with anti-PEG IgG antibody and not anti-PEG IgM antibody opsonization. This study highlights the need to carefully design and evaluate nanoparticle delivery systems for immunotherapy as anti-nanoparticle immune responses may challenge the therapeutic application.

AB - Systemic administration of toll-like receptor (TLR) agonists have demonstrated impressive preclinical results as an anti-cancer therapy due to their potent innate immune-stimulatory properties. The clinical advancement has, however, been hindered by severe adverse effects due to systemic activation of the immune system. Liposomal drug delivery systems may modify biodistribution, cellular uptake, and extend blood circulation, and thus, potentially enable systemic administration of TLR agonists at therapeutic doses. In this study, we investigated potential barriers for the administration of TLR agonists formulated in polyethylene glycosylated (PEGylated) liposomes with regards to liposome formulation, TLR agonist, administration route, administration schedule, biodistribution, blood clearance, and anti-PEG antibodies. We found that administration of TLR agonists formulated in PEGylated liposomes led to high anti-PEG antibody titers, which upon multiple intravenous administrations, resulted in accelerated blood clearance and acute hypersensitivity reactions. The latter was found to be associated with anti-PEG IgG antibody and not anti-PEG IgM antibody opsonization. This study highlights the need to carefully design and evaluate nanoparticle delivery systems for immunotherapy as anti-nanoparticle immune responses may challenge the therapeutic application.

KW - Anti-PEG antibodies

KW - Hypersensitivity

KW - Liposomes

KW - PEG

KW - PEGylated liposomes

KW - Systemic dosing

KW - TLRs

KW - Toll-like receptor agonists

U2 - 10.1016/j.jconrel.2021.12.033

DO - 10.1016/j.jconrel.2021.12.033

M3 - Journal article

C2 - 34973307

AN - SCOPUS:85122920519

VL - 342

SP - 337

EP - 344

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -

ID: 290734163