期刊
BRITISH JOURNAL OF CANCER
卷 103, 期 6, 页码 827-836出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6605832
关键词
glioblastoma; A1 domain of tenascin-C; interleukin-2; immunocytokines; temozolomide
类别
资金
- Swiss National Science Foundation [PMCDB-118729]
- ETH Zurich
- Swiss Cancer League
- SwissBridge Foundation
- Stammbach Foundation
- AIRC (Associazione Italiana Ricerca sul Cancro)
- Italo Monzino Foundation
- European Union
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 mu 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. British Journal of Cancer (2010) 103, 827-836. doi:10.1038/sj.bjc.6605832 www.bjcancer.com Published online 24 August 2010 (C) 2010 Cancer Research UK
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