Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized

Stone, Cosby A.; Liu, Yiwei; Relling, Mary V.; Krantz, Matthew S.; Pratt, Amanda; Abreo, Andrew; Hemler, Jonathan A.; Phillips, Elizabeth

doi:10.1016/j.jaip.2018.12.003

Cited by 293 publications

(443 citation statements)

References 24 publications

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“…Although PEGylation decreased immunogenicity compared with native L-ASP (Fig 1), PEG itself is becoming increasingly recognized as an antigen. 14,28 Anti-PEG was the predominant component (96%) of anti-PEG-ASP ( Fig 5 and Data Supplement), as was reported for pegloticase for gout. 29 Prevalence of anti-PEG in patients with ALL has not been extensively reported, but in the general population it has been reported to be as high as 10% to 30%.…”

Section: Antibodies Were Primarily Directed At Pegsupporting

confidence: 67%

Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge

Liu

Smith

Panetta

et al. 2019

JCO

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100

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PURPOSE Pegaspargase (PEG-ASP) has largely replaced native Escherichia coli asparaginase (L-ASP) in the treatment of acute lymphoblastic leukemia because of its longer half-life and lower immunogenicity. Risk factors for allergic reactions to PEG-ASP remain unclear. Here, we identify risk factors for reactions in a front-line acute lymphoblastic leukemia trial and assess the usefulness of serum antibodies for diagnosing allergy and predicting rechallenge outcome. PATIENTS AND METHODS PEG-ASP was administered to 598 patients in St Jude’s Total XVI study. Results were compared with Total XV study ( ClinicalTrials.gov identifiers: NCT00549848 and NCT00137111 ), which used native L-ASP. Serum samples (n = 5,369) were analyzed for anti–PEG-ASP immunoglobulin G by enzyme-linked immunosorbent assay. Positive samples were tested for anti–polyethylene glycol (PEG) and anti–L-ASP. We analyzed potential risk factors for reactions and associations between antibodies and reactions, rechallenge outcomes, and PEG-ASP pharmacokinetics. RESULTS Grade 2 to 4 reactions were less common in the Total XVI study with PEG-ASP (81 [13.5%] of 598) than in the Total XV study with L-ASP (169 [41.2%] of 410; P = 1.4 × 10−23). For Total XVI, anti-PEG, not anti–L-ASP, was the predominant component of anti–PEG-ASP antibodies (96%). In a multivariable analysis, more intrathecal therapy (IT) predicted fewer reactions ( P = 2.4 × 10−5), which is consistent with an immunosuppressant contribution of IT. Anti–PEG-ASP was associated with accelerated drug clearance ( P = 5.0 × 10−6). Failure of rechallenge after initial reactions was associated with anti–PEG-ASP ( P = .0078) and was predicted by the occurrence of angioedema with first reaction ( P = .01). CONCLUSION Less IT therapy was the only independent clinical risk factor for reactions to PEG-ASP. PEG, and not L-ASP, is the major antigen that causes allergic reactions. Anti–PEG-ASP has utility in predicting and confirming clinical reactions to PEG-ASP as well as in identifying patients who are most likely to experience failure with rechallenge.

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Section: Antibodies Were Primarily Directed At Pegsupporting

confidence: 67%

Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge

Liu

Smith

Panetta

et al. 2019

JCO

Self Cite

100

View full text Add to dashboard Cite

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“…For this reason, the PLGA nanoparticles proposed in our work were developed by using the poloxamer 188 as a stabilizer because it can confer long circulating properties to the particles, avoiding the use of PEG [30,31]. It is important to evidence that DMSO (alone or in combination with 2-hydroxypropyl-β-cyclodextrin) and a surfactant-based system made up of Tween 80 and PEG, which have been used to solubilize the drug ("free JQ1") in the in vitro and in vivo experiments [32,33], are mixtures associated with several adverse events on humans. Thus, their use is discouraged by the FDA reports.…”

Section: Discussionmentioning

confidence: 99%

Nanoparticles Loaded with the BET Inhibitor JQ1 Block the Growth of Triple Negative Breast Cancer Cells In Vitro and In Vivo

Maggisano

Celano

Malivindi

et al. 2019

Cancers

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Inhibition of bromo-and extra-terminal domain (BET) proteins, epigenetic regulators of genes involved in cell viability, has been efficiently tested in preclinical models of triple negative breast cancer (TNBC). However, the use of the selective BET-inhibitor JQ1 on humans is limited by its very short half-life. Herein, we developed, characterized and tested a novel formulation of nanoparticles containing JQ1 (N-JQ1) against TNBC in vitro and in vivo. N-JQ1, prepared using the nanoprecipitation method of preformedpoly-lactid-co-glycolic acid in an aqueous solution containing JQ1 and poloxamer-188 as a stabilizer, presented a high physico-chemical stability. Treatment of MDA-MB 157 and MDA-MB 231 TNBC cells with N-JQ1 determined a significant decrease in cell viability, adhesion and migration. Intra-peritoneal administration (5 days/week for two weeks) of N-JQ1 in nude mice hosting a xenograft TNBC after flank injection of MDA-MB-231 cells determined a great reduction in the growth and vascularity of the neoplasm. Moreover, the treatment resulted in a minimal infiltration of nearby tissues. Finally, the encapsulation of JQ1 in nanoparticles improved the anticancer efficacy of this epigenetic compound against TNBC in vitro and in vivo, opening the way to test it in the treatment of TNBC.

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“…Furthermore, they describe the role of clusterin in the regulation of complement activation as one that accelerates the formation of one of its components, namely sC5b-9. Anti-PEG IgG and IgE production and their role in the development of immediate hypersensitivity [65] or complement-activation-related pseudo-allergy (CARPA) [66] suggest that caution be exercised in the clinical use of PEGylated NMs.…”

Section: Limitations Of Protein-adsorption-mediated Targetingmentioning

confidence: 99%

Protein Adsorption: A Feasible Method for Nanoparticle Functionalization?

2019

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Nanomaterials are now well-established components of many sectors of science and technology. Their sizes, structures, and chemical properties allow for the exploration of a vast range of potential applications and novel approaches in basic research. Biomedical applications, such as drug or gene delivery, often require the release of nanoparticles into the bloodstream, which is populated by blood cells and a plethora of small peptides, proteins, sugars, lipids, and complexes of all these molecules. Generally, in biological fluids, a nanoparticle’s surface is covered by different biomolecules, which regulate the interactions of nanoparticles with tissues and, eventually, their fate. The adsorption of molecules onto the nanomaterial is described as “corona” formation. Every blood particulate component can contribute to the creation of the corona, although small proteins represent the majority of the adsorbed chemical moieties. The precise rules of surface-protein adsorption remain unknown, although the surface charge and topography of the nanoparticle seem to discriminate the different coronas. We will describe examples of adsorption of specific biomolecules onto nanoparticles as one of the methods for natural surface functionalization, and highlight advantages and limitations. Our critical review of these topics may help to design appropriate nanomaterials for specific drug delivery.

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Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized

Cited by 293 publications

References 24 publications

Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge

Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge

Nanoparticles Loaded with the BET Inhibitor JQ1 Block the Growth of Triple Negative Breast Cancer Cells In Vitro and In Vivo

Protein Adsorption: A Feasible Method for Nanoparticle Functionalization?

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