An engineered antibody-interleukin-12 fusion protein with enhanced tumor vascular targeting properties

Int J Cancer. 2006 Nov 1;119(9):2205-12. doi: 10.1002/ijc.22101.


The antibody-mediated targeted delivery of interleukin-12 (IL12) to the EDB domain of fibronectin, a marker of angiogenesis, is a promising avenue for enhancing the therapeutic index of this anti-cancer cytokine. Previous experiments, based on sequential fusion of a single-chain IL12 derivative to the anti-EDB antibody fragment scFv(L19) had yielded a therapeutic fusion protein [IL12-scFv(L19)-FLAG], which displayed an impressive therapeutic activity in murine models of cancer, in spite of a tumor uptake, which was less efficient compared to the parental unmodified scFv(L19). In this article, we describe the comparative analysis of 3 recombinant fusion proteins comprising the scFv(L19) and IL12 moieties. One of them, in which the p40 and p35 form a covalent heterodimer and in which each subunit is fused to a molecule of scFv(L19), displays an excellent tumor targeting performance in vivo, as assessed by quantitative biodistribution analysis, and a potent anti-tumor effect, superior to the one of IL12-scFv(L19)-FLAG. These results may have a clinical impact, considering the fact that the tumor targeting ability of scFv(L19) in patients with cancer has been demonstrated using scintigraphic methods, and that 2 scFv(L19)-based antibody-cytokine fusion are currently entering clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Interleukin-12 / genetics
  • Interleukin-12 / therapeutic use*
  • Kidney
  • Mice
  • Neoplasms / blood supply*
  • Neovascularization, Pathologic / prevention & control*
  • Protein Engineering / methods
  • Recombinant Fusion Proteins / therapeutic use*


  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • Interleukin-12