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Combined anti-C1-INH and radiotherapy against glioblastoma

Liljedahl, Emma LU ; Konradsson, Elise LU ; Gustafsson, Emma LU ; Jonsson, Karolina Förnvik LU orcid ; Olofsson, Jill K. ; Osther, Kurt LU ; Ceberg, Crister LU orcid and Redebrandt, Henrietta Nittby LU (2023) In BMC Cancer 23(1).
Abstract

Background: A more effective immune response against glioblastoma is needed in order to achieve better tumor control. Radiotherapy can induce anti-tumor mediated immune reactions, in addition to its dose response effects. The complement system can function as a bridge between innate and adaptive immune responses. Combining radiotherapy and complement activating therapy is theoretically interesting. Methods: Radiotherapy at 8 Gy × 2 was combined with treatment against C1-inhibitor (C1-INH), a potent inhibitor of activation of the classical pathway of the complement system. Anti-C1-INH was delivered as intratumoral injections. Fully immunocompetent Fischer 344 rats with NS1 glioblastoma tumors were treated. Survival was monitored as... (More)

Background: A more effective immune response against glioblastoma is needed in order to achieve better tumor control. Radiotherapy can induce anti-tumor mediated immune reactions, in addition to its dose response effects. The complement system can function as a bridge between innate and adaptive immune responses. Combining radiotherapy and complement activating therapy is theoretically interesting. Methods: Radiotherapy at 8 Gy × 2 was combined with treatment against C1-inhibitor (C1-INH), a potent inhibitor of activation of the classical pathway of the complement system. Anti-C1-INH was delivered as intratumoral injections. Fully immunocompetent Fischer 344 rats with NS1 glioblastoma tumors were treated. Survival was monitored as primary outcome. Models with either intracranial or subcutaneous tumors were evaluated separately. Results: In the intracranial setting, irradiation could prolong survival, but there was no additional survival gain as a result of anti-C1-INH treatment. In animals with subcutaneous tumors, combined radio-immunotherapy with anti-C1-INH and irradiation at 8 Gy × 2 significantly prolonged survival compared to control animals, whereas irradiation or anti-C1-INH treatment as single therapies did not lead to significantly increased survival compared to control animals. Conclusions: Anti-C1-INH treatment could improve the efficacy of irradiation delivered at sub-therapeutic doses and delay tumor growth in the subcutaneous tumor microenvironment. In the intracranial setting, the doses of anti-C1-INH were not enough to achieve any survival effect in the present setting.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Complement system, Glioblastoma, Radiotherapy
in
BMC Cancer
volume
23
issue
1
article number
106
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85147124539
  • pmid:36717781
ISSN
1471-2407
DOI
10.1186/s12885-023-10583-1
language
English
LU publication?
yes
id
919e565f-132a-433c-b1b0-96a81f7c4fa9
date added to LUP
2023-02-09 15:07:22
date last changed
2024-04-16 07:22:41
@article{919e565f-132a-433c-b1b0-96a81f7c4fa9,
  abstract     = {{<p>Background: A more effective immune response against glioblastoma is needed in order to achieve better tumor control. Radiotherapy can induce anti-tumor mediated immune reactions, in addition to its dose response effects. The complement system can function as a bridge between innate and adaptive immune responses. Combining radiotherapy and complement activating therapy is theoretically interesting. Methods: Radiotherapy at 8 Gy × 2 was combined with treatment against C1-inhibitor (C1-INH), a potent inhibitor of activation of the classical pathway of the complement system. Anti-C1-INH was delivered as intratumoral injections. Fully immunocompetent Fischer 344 rats with NS1 glioblastoma tumors were treated. Survival was monitored as primary outcome. Models with either intracranial or subcutaneous tumors were evaluated separately. Results: In the intracranial setting, irradiation could prolong survival, but there was no additional survival gain as a result of anti-C1-INH treatment. In animals with subcutaneous tumors, combined radio-immunotherapy with anti-C1-INH and irradiation at 8 Gy × 2 significantly prolonged survival compared to control animals, whereas irradiation or anti-C1-INH treatment as single therapies did not lead to significantly increased survival compared to control animals. Conclusions: Anti-C1-INH treatment could improve the efficacy of irradiation delivered at sub-therapeutic doses and delay tumor growth in the subcutaneous tumor microenvironment. In the intracranial setting, the doses of anti-C1-INH were not enough to achieve any survival effect in the present setting.</p>}},
  author       = {{Liljedahl, Emma and Konradsson, Elise and Gustafsson, Emma and Jonsson, Karolina Förnvik and Olofsson, Jill K. and Osther, Kurt and Ceberg, Crister and Redebrandt, Henrietta Nittby}},
  issn         = {{1471-2407}},
  keywords     = {{Complement system; Glioblastoma; Radiotherapy}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Cancer}},
  title        = {{Combined anti-C1-INH and radiotherapy against glioblastoma}},
  url          = {{http://dx.doi.org/10.1186/s12885-023-10583-1}},
  doi          = {{10.1186/s12885-023-10583-1}},
  volume       = {{23}},
  year         = {{2023}},
}