Impact of anti-PEG IgM antibodies on the pharmacokinetics of pegylated asparaginase preparations in mice.

@article{Poppenborg2016ImpactOA,
  title={Impact of anti-PEG IgM antibodies on the pharmacokinetics of pegylated asparaginase preparations in mice.},
  author={Sabine Poppenborg and Julia G. Wittmann and Wolfgang Walther and Gunda Brandenburg and Ralf Kr{\"a}hmer and Joachim Baumgart and Frank Leenders},
  journal={European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences},
  year={2016},
  volume={91},
  pages={
          122-30
        }
}
  • Sabine Poppenborg, J. Wittmann, F. Leenders
  • Published 25 August 2016
  • Biology
  • European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated E. coli asparaginase in children with acute lymphocytic leukemia.
TLDR
Pre-existing anti-PEG antibodies did not inhibit PEG-ASnase activity but significantly reduced PEGASNase activity levels in a concentration dependent manner, and pre-existinganti-Peg antibodies were significantly associated with firstexposure hypersensitivity reactions (CTCAE grade 2).
Impact of Antibodies Against Polyethylene Glycol on the Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukaemia: A Population Pharmacokinetic Approach
TLDR
Pre-existing antibodies against PEG-ASNase significantly increased the initial clearance in a subgroup of patients showing high antibody levels, and the combination of both isotypes did not provide additional information compared to anti-PEG IgMprior alone.
Pre-existing anti-polyethylene glycol antibody reduces the therapeutic efficacy and pharmacokinetics of PEGylated liposomes
TLDR
Pre-αPEG may have potential as a marker to aid development of personalized therapy using LipoDox and achieve optimal therapeutic efficacy and biodistribution results suggested that pre- αPEG Ab can significantly reduce tumor accumulation and accelerate blood clearance from the spleen.
Tolerogenic Immunomodulation by PEGylated Antigenic Peptides
TLDR
PEGylation of antigenic peptides is an effective and feasible strategy to improve Treg-inducing, peptide-based vaccines with potential use for the treatment of autoimmune diseases, allergies, and transplant rejection.
Prevention of EAE by PEGylated Antigenic Peptides
TLDR
PEGylation of antigenic peptides is an effective and feasible strategy to improve tolerogenic (Treg-inducing) peptide-based vaccines, but application in overt disease might require modifications or combination therapies that simultaneously suppress effector mechanisms.
Prevention of EAE by tolerogenic vaccination with PEGylated antigenic peptides
TLDR
PEGylation of antigenic peptides is an effective and feasible strategy to improve tolerogenic (Treg-inducing) peptide-based vaccines, but application for immunotherapy of overt disease might require modifications or combination therapies that simultaneously suppress effector mechanisms.
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TLDR
PEGylation of therapeutic agents will continue to be of significant value in medicine to reduce immunogenicity, antigenicity and toxicity as well as markedly reducing renal clearance, while maintaining drug efficacy.
Role of the Methoxy Group in Immune Responses to mPEG-Protein Conjugates
TLDR
Results are consistent with the hypothesis that antibodies with high affinity for methoxy groups contribute to the loss of efficacy of mPEG conjugates, especially if multiply-PEGylated.
Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents
TLDR
Animal studies clearly showed that uricase, ovalbumin and some other PEGylated agents can elicit antibody formation against PEG (anti-PEG), which raises concerns regarding the efficacy of PEG-conjugated drugs for a subset of patients.
A prospective study on drug monitoring of PEGasparaginase and Erwinia asparaginase and asparaginase antibodies in pediatric acute lymphoblastic leukemia.
TLDR
The presence of asparaginase antibodies was related to allergies and silent inactivation, but with low specificity, and use of native E coli asparagenase in induction leads to high hypersensitivity rates to PEGas paraginase in intensification.
Anti-PEG IgM Response against PEGylated Liposomes in Mice and Rats
TLDR
The present study demonstrated that the spleen is a major organ involved in the secretion of anti-PEG IgM in mice and rats, and suggests that PEGylated liposomes may function as a type-2, T-cell-independent antigen (TI-2 antigen) duringAnti-Peg IgM production.
Comparison of Native E. coli and PEG Asparaginase Pharmacokinetics and Pharmacodynamics in Pediatric Acute Lymphoblastic Leukemia
TLDR
The modeling suggests that by modifying dosages, comparable ASN depletion is achievable with both preparations, and it is suggested that by changing dosage levels, comparable Asparagine (ASN) depletion can be achieved by both preparations.
Intravenous administration of polyethylene glycol-coated (PEGylated) proteins and PEGylated adenovirus elicits an anti-PEG immunoglobulin M response.
TLDR
It appears that anti-PEG IgMs can be produced by the systemic administration of a P EGylated substance and may limit the efficacy of PEGylated substances such as proteins, Ad vector and nanoparticles, due to a cross-reactivity seen in some patients.
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