Limits...
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 - Br. J. Cancer (2010)

Bottom Line: A quantitative biodistribution confirmed the preferential tumour accumulation of radiolabelled F16-IL2.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.

View Article: PubMed Central - PubMed

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.

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.

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.

Show MeSH

Related in: MedlinePlus

Immunofluorescence analysis of F16–IL2 fusion protein localisation in subcutaneous (A) and intracranial (B) glioblastoma xenografts, 24 h after the third injection of therapeutic agents (serial tissue sections). Scale bars indicate 100 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2966626&req=5

fig4: Immunofluorescence analysis of F16–IL2 fusion protein localisation in subcutaneous (A) and intracranial (B) glioblastoma xenografts, 24 h after the third injection of therapeutic agents (serial tissue sections). Scale bars indicate 100 μm.

Mentions: We performed an ex vivo localisation of the F16–IL2 fusion protein in subcutaneous and intracranial glioblastoma xenografts collected from BALB/c nude mice, which were obtained after three drug administrations of F16–IL2 or the combination of F16–IL2 and temozolomide. The staining for human IL-2 revealed a selective and comparable accumulation of the F16–IL2 immunocytokine around tumour vascular structures in both subcutaneous (A) and intracranial (B) xenografts (Figure 4).


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 - Br. J. Cancer (2010)

Immunofluorescence analysis of F16–IL2 fusion protein localisation in subcutaneous (A) and intracranial (B) glioblastoma xenografts, 24 h after the third injection of therapeutic agents (serial tissue sections). Scale bars indicate 100 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966626&req=5

fig4: Immunofluorescence analysis of F16–IL2 fusion protein localisation in subcutaneous (A) and intracranial (B) glioblastoma xenografts, 24 h after the third injection of therapeutic agents (serial tissue sections). Scale bars indicate 100 μm.
Mentions: We performed an ex vivo localisation of the F16–IL2 fusion protein in subcutaneous and intracranial glioblastoma xenografts collected from BALB/c nude mice, which were obtained after three drug administrations of F16–IL2 or the combination of F16–IL2 and temozolomide. The staining for human IL-2 revealed a selective and comparable accumulation of the F16–IL2 immunocytokine around tumour vascular structures in both subcutaneous (A) and intracranial (B) xenografts (Figure 4).

Bottom Line: A quantitative biodistribution confirmed the preferential tumour accumulation of radiolabelled F16-IL2.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.

View Article: PubMed Central - PubMed

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.

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.

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.

Show MeSH
Related in: MedlinePlus