Ganglioside inserted into PEGylated liposome attenuates anti-PEG immunity

Mima, Yu; Lila, Amr S. Abu; Shimizu, Taro; Ukawa, Masami; Ando, Hidenori; Kurata, Yasuko; Ishida, Tatsuhiro

doi:10.1016/j.jconrel.2017.01.040

Cited by 46 publications

(31 citation statements)

References 51 publications

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“…This strategy was more efficacious to decrease the anti‐PEG antibodies production. [ 115 ] In this perspective, we agree that this strategy can decrease the induction of IgM and IgG production in rats that did not show pre‐existing anti‐PEG antibodies, because they have never, or slightly interacted with PEGylated products during their lifetime. However, further studies are needed to confirm this trend in the presence of pre‐existing anti‐PEG antibodies in animal models.…”

Section: Strategies To Overcome Side Effects Of Pegmentioning

confidence: 57%

“…The use of gangliosides has been rediscovered by Ishida and co‐workers, who recently proposed their addition into the PEGylated liposomes. [ 115 ] Gangliosides are expressed in the cellular membranes of all tissues, particularly in the central nervous system and tumors. They have several functions, including modulation of the immune system.…”

Section: Strategies To Overcome Side Effects Of Pegmentioning

confidence: 99%

See 1 more Smart Citation

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

d’Avanzo

Celia

Barone

et al. 2020

Advanced Therapeutics

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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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Section: Strategies To Overcome Side Effects Of Pegmentioning

confidence: 57%

Section: Strategies To Overcome Side Effects Of Pegmentioning

confidence: 99%

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

d’Avanzo

Celia

Barone

et al. 2020

Advanced Therapeutics

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show abstract

“…Insertion of gangliosides from a porcine brain (oligoglycosylceramides; a mixture of GM1, GD1a, GD1b and GT1b, containing sialic acid) into PEGylated liposomes at a concentration of 10% of the total phospholipids also shows activity in reducing the ABC effect [112]. This is attributed to the immunosuppressive effect of gangliosides, functioning as Siglec ligands (lectin-like adhesion proteins on macrophages) on reactive B cells that result in B cell tolerance and decreased anti-PEG IgM production.…”

Section: Insertion Of Gangliosides Into Pegylated Liposomesmentioning

confidence: 99%

PEGylated liposomes: immunological responses

Mohamed

Lila

Shimizu

et al. 2019

Science and Technology of Advanced Materials

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335

309

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A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are nonimmunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.

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“…There are multiple approaches under investigation to reduce PEG-associated immunity. For instance, it was shown that the incorporation of gangliosides (a type of glycolipids natively present in cell membranes) into PEGylated liposomes reduced production of anti-PEG IgM in challenged mice, but only when both ligands were presented on the same particle (Mima et al, 2017). When these ganglioside-containing PEGylated liposomes were administered as a pretreatment, they also reduced anti-IgM production upon subsequent treatment with PEGylated liposomes without gangliosides.…”

Section: Alternatives To Pegmentioning

confidence: 99%

Overcoming Physiological Barriers to Nanoparticle Delivery—Are We There Yet?

Thomas

Weber

2019

Front. Bioeng. Biotechnol.

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The exploitation of nanosized materials for the delivery of therapeutic agents is already a clinical reality and still holds unrealized potential for the treatment of a variety of diseases. This review discusses physiological barriers a nanocarrier must overcome in order to reach its target, with an emphasis on cancer nanomedicine. Stages of delivery include residence in the blood stream, passive accumulation by virtue of the enhanced permeability and retention effect, diffusion within the tumor lesion, cellular uptake, and arrival at the site of action. We also briefly outline strategies for engineering nanoparticles to more efficiently overcome these challenges: Increasing circulation half-life by shielding with hydrophilic polymers, such as PEG, the limitations of PEG and potential alternatives, targeting and controlled activation approaches. Future developments in these areas will allow us to harness the full potential of nanomedicine.

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Ganglioside inserted into PEGylated liposome attenuates anti-PEG immunity

Cited by 46 publications

References 51 publications

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

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

PEGylated liposomes: immunological responses

Overcoming Physiological Barriers to Nanoparticle Delivery—Are We There Yet?

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