Document Detail


Novel immunosuppressant agents targeting activated lymphocytes by biocompatible MPC polymer conjugated with interleukin-2.
MedLine Citation:
PMID:  17299267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The immunopharmacological profile of novel biocompatible water-soluble interleukin-2 (IL-2)-conjugated 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer immunosuppressive agents was established. MPC-co-n- butyl methacrylate (BMA)-co-p-nitrophenylcarbonyloxyethyl methacrylate (NPMA) (PMBN) was prepared as a backbone for these novel agents. PMBN contained MPC as a biocompatible unit, BMA as a hydrophobic domain in water, and NPMA as an immobilizable unit with IL-2. This research showed that proliferation of cell lines with high-affinity IL-2 receptors derived from T cell malignancies were suppressed by the PMBN conjugated with IL-2 (PMBN-IL2 conjugate) incorporating paclitaxel (PTX) and cyclosporin A at lower concentrations than used conventionally. PMBN-IL2 conjugates incorporating PTX also inhibited the proliferation of responder cells in a human mixed lymphocyte culture at a lower concentration than unconjugated drug. However, PMBN-IL2 conjugates incorporating FK506 inhibited proliferation no more than FK506 alone. The PMBN-IL2 conjugate with PTX may therefore be useful for selectively eliminating activated lymphocytes that hyperproduce high-affinity IL-2 receptors. As an entirely human 'immunotoxin analogue' it may not be associated with the dose-limiting toxicity and immunogenicity of conventional immunotoxins.
Authors:
N Chiba; M Ueda; T Shimada; H Jinno; J Watanabe; K Ishihara; M Kitajima
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Publication Detail:
Type:  Journal Article     Date:  2007-02-13
Journal Detail:
Title:  European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes     Volume:  39     ISSN:  0014-312X     ISO Abbreviation:  Eur Surg Res     Publication Date:  2007  
Date Detail:
Created Date:  2007-03-30     Completed Date:  2007-05-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0174752     Medline TA:  Eur Surg Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  103-10     Citation Subset:  IM    
Copyright Information:
Copyright 2007 S. Karger AG, Basel.
Affiliation:
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacokinetics
Biocompatible Materials / chemical synthesis,  pharmacokinetics
Cell Division / drug effects
Cell Line, Tumor
Cyclosporine / pharmacokinetics*
Drug Delivery Systems / methods
Humans
Hydrophobicity
Immunosuppressive Agents / pharmacokinetics*
Interleukin-2 / chemical synthesis,  pharmacokinetics*
Lymphocyte Activation / drug effects*
Lymphocyte Culture Test, Mixed
Methacrylates / chemical synthesis,  pharmacokinetics*
Paclitaxel / pharmacokinetics
Polyethylene Glycols / chemical synthesis,  pharmacokinetics*
Solubility
T-Lymphocytes / drug effects*,  immunology,  metabolism
Tacrolimus / pharmacokinetics
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Biocompatible Materials; 0/Immunosuppressive Agents; 0/Interleukin-2; 0/Methacrylates; 0/Polyethylene Glycols; 0/poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-nitrophenyloxycarbonyl polyethyleneglycol methacrylate); 109581-93-3/Tacrolimus; 33069-62-4/Paclitaxel; 59865-13-3/Cyclosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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