Novel immunosuppressant agents targeting activated lymphocytes by biocompatible MPC polymer conjugated with interleukin-2

N. Chiba, M. Ueda, T. Shimada, H. Jinno, J. Watanabe, K. Ishihara, M. Kitajima

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)103-110
Number of pages8
JournalEuropean Surgical Research
Volume39
Issue number2
DOIs
Publication statusPublished - 2007 Mar 1

Keywords

  • Immunosuppressive agents
  • Interleukin-2
  • Interleukin-2 receptor, high affinity
  • MPC polymer

ASJC Scopus subject areas

  • Surgery

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