The immunocytokine F8-IL2 improves the therapeutic performance of sunitinib in a mouse model of renal cell carcinoma

J Urol. 2010 Dec;184(6):2540-8. doi: 10.1016/j.juro.2010.07.030. Epub 2010 Oct 28.


Purpose: We investigated the therapeutic action of F8-IL2, a fusion protein consisting of the F8 antibody specific to the alternatively spliced extradomain-A of fibronectin, in diabody format and of human interleukin-2 in the Caki-1 (ATCC®) model of human renal cell carcinoma grafted subcutaneously in nude mice.

Materials and methods: F8-IL2 was cloned, expressed in CHO cells and purified to homogeneity. This immunocytokine was administered alone or combined with 3 standard drugs commonly used as therapy for kidney cancer, including sunitinib, sorafenib and interferon-α, in 2 sets of doses and treatment schedules.

Results: Neither F8-IL2 nor any other therapeutic agent cured tumor bearing mice when used as a single agent. The best therapeutic results were observed for the combination of sunitinib with F8-IL2 in a continuous administration schedule, which yielded a 28% cure rate and substantial tumor growth retardation.

Conclusions: Considering that recombinant interleukin-2 based immunocytokines are now being investigated in several clinical trials in patients with cancer alone or combined with chemotherapy our preclinical results provide a motivation to study F8-IL2 combined with sunitinib in clinical trials in patients with kidney cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Disease Models, Animal*
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Indoles / therapeutic use*
  • Interleukin-2 / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pyrroles / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Sunitinib


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • F8 monoclonal antibody
  • F8-IL2 immunocytokine
  • Indoles
  • Interleukin-2
  • Pyrroles
  • Recombinant Fusion Proteins
  • Sunitinib