Oncotarget

Research Papers:

Anti-C1-inactivator treatment of glioblastoma

Karolina Förnvik _, Jonatan Ahlstedt, Kurt Osther, Leif G. Salford and Henrietta Nittby Redebrandt

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Oncotarget. 2018; 9:37421-37428. https://doi.org/10.18632/oncotarget.26456

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Abstract

Karolina Förnvik1,2, Jonatan Ahlstedt1, Kurt Osther1, Leif G. Salford1 and Henrietta Nittby Redebrandt1,3

1The Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Lund, Sweden

2Department of Clinical Chemistry, Skåne University Hospital, Lund, Sweden

3Department of Neurosurgery, Skåne University Hospital, Lund, Sweden

Correspondence to:

Karolina Förnvik, email: karolina.fornvik@med.lu.se

Keywords: complement; C1-inactivator; glioblastoma

Received: September 13, 2018     Accepted: November 26, 2018     Published: December 21, 2018

ABSTRACT

Purpose: Glioblastoma multiforme (GBM) or astrocytoma grade IV is the most common type of primary brain tumor in adults. In the present study, we investigate the role of the complement system in the glioblastoma situation in an experimental model, since we have previously been able to show a blockade of this system in the glioblastoma setting.

Technique and results: A GFP-positive glioblastoma cell line was used to induce glioblastomas subcutaneously in rats (n=42). Antibodies against C1-Inactivator (C1-IA) were used to try to re-activate the complement system. We were able to demonstrate an increased survival in rats treated with anti-C1-IA with an intratumoral route, and we could establish the same the results in a second series. Serum analyses revealed decreased levels of IL-1b and GM-CSF in animals 24 days after tumor cell inoculation in the anti-C1-IA group when compared to controls. Immunohistochemistry revealed decreased expression of C1-IA following treatment.

Interpretation: These results are in line with our previous work showing an upregulation of C1-IA, which is able to block the classical complement pathway, in glioblastomas. Treatment with antibodies against C1-IA seems to be beneficial in the glioblastoma situation, and no side effects could be seen in our experiments.


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