PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner

Ishida, Tatsuhiro; Wang, XinYu; Shimizu, Taro; Nawata, Kosuke; Kiwada, Hiroshi

doi:10.1016/j.jconrel.2007.05.015

Cited by 382Nanoparticle-Based Drug DeliveryImmunotherapy and Immune ResponsesRNA Interference and Gene Delivery

PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner

Ishida, Tatsuhiro, Wang, XinYu, Shimizu, Taro, Nawata, Kosuke, Kiwada, Hiroshi·2007·Journal of Controlled Release

DOI 10.1016/j.jconrel.2007.05.015

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Abstract

We recently reported that intravenous injections of "empty" PEGylated liposomes without encapsulated or surface coupled proteins elicit a PEG-specific IgM response in rats. In the present study, simultaneous weak anti-PEG IgG and strong anti-PEG IgM responses were detected following intravenous injections of "empty" PEGylated liposomes. The pattern of immune response appears to differ from the classic primary response against T cell-dependent (TD) antigens. The anti-PEG IgM response was detected in T-cell deficient nude BALB/c mice following intravenous injection of "empty" PEGylated liposomes, suggesting that "empty" PEGylated liposomes initiate the immune response against PEG in a T cell-independent manner. In vitro splenic lymphocytes-proliferation assay indicated that TNP-LPS, a typical type 1 T cell-independent (TI) antigen (TI-1 antigen), significantly primed the proliferation, while TNP-Ficoll, a typical type 2 TI antigen (TI-2 antigen), and "empty" PEGylated liposomes did not prime any proliferation under these experimental conditions. In addition, in splenic marginal zone (MZ) B-cell-depleted rats, the anti-PEG IgM response was diminished, while the immune reactions against TNP-BSA (a TD antigen) and TNP-LPS (TI-1 antigen) were not diminished. These results demonstrate that "empty" PEGylated liposomes may promote the immune response against PEG as a result of priming the activation of MZ B cells, as TI-2 antigen promotes a specific IgM response. In conclusion, although the mechanistic details behind the immune reaction against "empty" PEGylated liposomes are not yet clear, the liposomes elicit an anti-PEG IgM response in a T cell-independent manner and appear to be a TI-2 antigen, and splenic MZ B cells may be essential for the immune response against "empty" PEGylated liposomes.

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Some reports demonstrated generation of PEG-specific antibodies after administration of PEG-coated liposomes.
“However, some reports also demonstrated the generation of PEG-specific antibodies after administration of PEG-coated liposomes [153, 154].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [153]

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Authors: Ishida, T., Wang, X., Shimizu, T., Nawata, K., & Kiwada, H.
Affiliations: Tokushima University (JP)
Corresponding author: Kiwada, Hiroshi
ORCID: Ishida, Tatsuhiro
Shimizu, Taro
Venue: Journal of Controlled Release
Publisher: Elsevier BV
Published: 2007-10
Volume: 122
Issue: 3
Pages: 349-355
ISSN: 0168-3659 (ISSN-L)
DOI: 10.1016/j.jconrel.2007.05.015
OpenAlex: W2087167636
Cited by: 382
References: 45
Citations by year: 2026: 13 · 2025: 20 · 2024: 14 · 2023: 28 · 2022: 20 · 2021: 23 · 2020: 25 · 2019: 13 · 2018: 32 · 2017: 22 · 2016: 24 · 2015: 29 · 2014: 24 · 2013: 29 · 2012: 25
FWCI: 4.91
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Controlled Release (publishedVersion)
PubMed (publishedVersion)
Funders: Kao Foundation for Arts and Sciences
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords: PEGylated liposomes, T cell-independent immunity, marginal zone B cells, nude mice, TNP-LPS, TNP-Ficoll, splenocyte proliferation, intravenous injection
MeSH terms: Animals, Antigens, T-Independent, Cyclophosphamide, Immunoglobulin G, Immunoglobulin M, Injections, Intravenous, Liposomes, Male, Mice, Inbred BALB C, Mice, Nude, Polyethylene Glycols, Spleen, T-Lymphocytes, Rats, Wistar, Cell Proliferation, Mice, Rats

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PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner

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