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

Katharina Frey, Christoph Schliemann, Kathrin Schwager, Raffaella Giavazzi, Manfred Johannsen, Dario Neri

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2540-2548
Number of pages9
JournalJournal of Urology
Volume184
Issue number6
DOIs
Publication statusPublished - Dec 2010

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Renal Cell Carcinoma
Interleukin-2
Kidney Neoplasms
Therapeutics
Appointments and Schedules
Clinical Trials
Neoplasms
CHO Cells
F8-IL2 immunocytokine
sunitinib
Fibronectins
Nude Mice
Interferons
Drug Therapy
Growth
Pharmaceutical Preparations
Proteins

Keywords

  • Carcinoma renal cell
  • Cytokines
  • Extracellular matrix proteins
  • F8 monoclonal antibody
  • Sunitinib

ASJC Scopus subject areas

  • Urology

Cite this

The immunocytokine F8-IL2 improves the therapeutic performance of sunitinib in a mouse model of renal cell carcinoma. / Frey, Katharina; Schliemann, Christoph; Schwager, Kathrin; Giavazzi, Raffaella; Johannsen, Manfred; Neri, Dario.

In: Journal of Urology, Vol. 184, No. 6, 12.2010, p. 2540-2548.

Research output: Contribution to journalArticle

Frey, Katharina ; Schliemann, Christoph ; Schwager, Kathrin ; Giavazzi, Raffaella ; Johannsen, Manfred ; Neri, Dario. / The immunocytokine F8-IL2 improves the therapeutic performance of sunitinib in a mouse model of renal cell carcinoma. In: Journal of Urology. 2010 ; Vol. 184, No. 6. pp. 2540-2548.
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