Novel IL-2-Poly(HPMA)Nanoconjugate Based Immunotherapy

J Biomed Nanotechnol. 2015 Sep;11(9):1662-73. doi: 10.1166/jbn.2015.2114.


Interleukin-2 (IL-2) possesses a strong stimulatory activity for activated T and NK cells and it is an attractive molecule for immunotherapy. Nevertheless, extremely short half-life and severe toxicities associated with high-dose IL-2 treatment are serious and limiting drawbacks. In order to increase IL-2 half-life in vivo, we covalently conjugated synthetic semitelechelic polymeric carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA) to IL-2. Thus, we synthesized IL-2-poly(HPMA) conjugate containing 2-3 polymer chains per IL-2 molecule in average. Such conjugate has lower biologic activity in comparison to IL-2 in vitro. However, it exerts much higher activity than IL-2 in vivo as shown by expansion of memory CD8+ T, NK, NKT, γδT and Treg cells. Moreover, IL-2-poly(HPMA) extremely effectively potentiates CD8+ T cell peptide-based vaccination. IL-2-poly(HPMA) shows also much longer half-time in circulation than IL-2 (-4 h versus -5 min). Collectively, modification of IL-2 with poly(HPMA) chains dramatically improves its potency and pharmacologic features in vivo, which have implications for immunotherapy. To our knowledge, this is the first proof-of-concept report of the use of polymer/protein modification of IL-2 to obtain more pronounced biological activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diffusion
  • Female
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Immunologic Factors / chemistry
  • Immunologic Factors / immunology
  • Immunologic Factors / therapeutic use
  • Immunotherapy / methods
  • Interleukin-2 / chemistry
  • Interleukin-2 / immunology*
  • Interleukin-2 / therapeutic use*
  • Male
  • Materials Testing
  • Methacrylates / chemistry*
  • Mice, Inbred C57BL
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Nanoconjugates / chemistry
  • Nanoconjugates / therapeutic use*
  • Nanoconjugates / ultrastructure
  • Particle Size
  • Surface Properties


  • Immunologic Factors
  • Interleukin-2
  • Methacrylates
  • Nanocapsules
  • Nanoconjugates
  • hydroxypropyl methacrylate