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Anti-C1-inactivator treatment of glioblastoma

Förnvik, Karolina LU ; Ahlstedt, Jonatan LU ; Osther, Kurt LU ; Salford, Leif G. LU and Redebrandt, Henrietta Nittby LU (2018) In Oncotarget 9(100). p.37421-37428
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.... (More)

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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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C1-inactivator, Complement, Glioblastoma
in
Oncotarget
volume
9
issue
100
pages
8 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85058842682
ISSN
1949-2553
DOI
10.18632/oncotarget.26456
language
English
LU publication?
yes
id
b6e72ffa-b23e-44bd-b5a3-690a987ee009
date added to LUP
2019-01-03 14:21:01
date last changed
2020-12-08 04:44:40
@article{b6e72ffa-b23e-44bd-b5a3-690a987ee009,
  abstract     = {<p>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.</p>},
  author       = {Förnvik, Karolina and Ahlstedt, Jonatan and Osther, Kurt and Salford, Leif G. and Redebrandt, Henrietta Nittby},
  issn         = {1949-2553},
  language     = {eng},
  number       = {100},
  pages        = {37421--37428},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Anti-C1-inactivator treatment of glioblastoma},
  url          = {http://dx.doi.org/10.18632/oncotarget.26456},
  doi          = {10.18632/oncotarget.26456},
  volume       = {9},
  year         = {2018},
}