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- Title
Novel Immunosuppressant Agents Targeting Activated Lymphocytes by Biocompatible MPC Polymer Conjugated with Interleukin-2.
- Authors
Chiba, N.; Ueda, M.; Shimada, T.; Jinno, H.; Watanabe, J.; Ishihara, K.; Kitajima, M.
- 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. Copyright © 2007 S. Karger AG, Basel
- Subjects
IMMUNOSUPPRESSIVE agents; LYMPHOCYTES; INTERLEUKIN-2; T cells; ANTIBODY-toxin conjugates; CYCLOSPORINE
- Publication
European Surgical Research, 2007, Vol 39, Issue 2, p103
- ISSN
0014-312X
- Publication type
Article
- DOI
10.1159/000099598