Combination of temozolomide with immunocytokine F16-IL2 for the treatment of glioblastoma

M. Pedretti, C. Verpelli, J. Mårlind, G. Bertani, C. Sala, D. Neri, L. Bello

Research output: Contribution to journalArticlepeer-review

Abstract

Background:Glioblastoma patients are still not cured by the treatments available at the moment. We investigated the therapeutic properties of temozolomide in combination with F16-IL2, a clinical-stage immunocytokine consisting of human interleukin (IL)-2 fused to the human antibody F16, specific to the A1 domain of tenascin-C.Methods:We conducted three preclinical therapy studies, using subcutaneous and intracranial U87MG glioblastoma tumours xenografted in BALB/c nude mice. The same therapeutic schedule was used, consisting of five total administrations every third day, of 0.525 mg temozolomide, 20 g F16-IL2, the combination, or the control solution.Results: Immunohistochemical analysis of U87MG xenografts and of human glioblastoma specimens showed selective tumour staining of F16. A quantitative biodistribution confirmed the preferential tumour accumulation of radiolabelled F16-IL2. In the study with subcutaneous xenografts, the combination of F16-IL2 with temozolomide induced complete remission of the animals, which remained tumour free for over 160 days. The same treatment led to a consistent size reduction of intracranial xenografts and to a longer survival of animals. The immunocytokine promoted the recruitment of leukocytes into tumours of both models.Conclusion:The combined use of temozolomide with F16-IL2 deserves clinical investigations, which will be facilitated by the excellent safety profile in cynomolgus monkeys, and by the fact that F16-IL2 is in clinical trials in patients with cancer.

Original languageEnglish
Pages (from-to)827-836
Number of pages10
JournalBritish Journal of Cancer
Volume103
Issue number6
DOIs
Publication statusPublished - Sep 7 2010

Keywords

  • A1 domain of tenascin-C
  • glioblastoma
  • immunocytokines
  • interleukin-2
  • temozolomide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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