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 language | English |
|---|---|
| Pages (from-to) | 827-836 |
| Number of pages | 10 |
| Journal | British Journal of Cancer |
| Volume | 103 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Sep 7 2010 |
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Keywords
- A1 domain of tenascin-C
- glioblastoma
- immunocytokines
- interleukin-2
- temozolomide
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Medicine(all)
Cite this
Combination of temozolomide with immunocytokine F16-IL2 for the treatment of glioblastoma. / Pedretti, M.; Verpelli, C.; Mårlind, J.; Bertani, G.; Sala, C.; Neri, D.; Bello, L.
In: British Journal of Cancer, Vol. 103, No. 6, 07.09.2010, p. 827-836.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Combination of temozolomide with immunocytokine F16-IL2 for the treatment of glioblastoma
AU - Pedretti, M.
AU - Verpelli, C.
AU - Mårlind, J.
AU - Bertani, G.
AU - Sala, C.
AU - Neri, D.
AU - Bello, L.
PY - 2010/9/7
Y1 - 2010/9/7
N2 - 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.
AB - 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.
KW - A1 domain of tenascin-C
KW - glioblastoma
KW - immunocytokines
KW - interleukin-2
KW - temozolomide
UR - http://www.scopus.com/inward/record.url?scp=77956450051&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956450051&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6605832
DO - 10.1038/sj.bjc.6605832
M3 - Article
C2 - 20736949
AN - SCOPUS:77956450051
VL - 103
SP - 827
EP - 836
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 6
ER -