title: Combination of temozolomide with immunocytokine F16-IL2 for the treatment of glioblastoma.
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 microg 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH-Swiss Federal Institute of Technology Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Pedretti
authors.forename: C
authors.initials: C
authors.lastname: Verpelli
authors.forename: J
authors.initials: J
authors.lastname: Mårlind
authors.forename: G
authors.initials: G
authors.lastname: Bertani
authors.forename: C
authors.initials: C
authors.lastname: Sala
authors.forename: D
authors.initials: D
authors.lastname: Neri
authors.forename: L
authors.initials: L
authors.lastname: Bello
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D000077204:Temozolomide; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D003606:Dacarbazine; D000077204:Temozolomide