Combined anti-C1-INH and radiotherapy against glioblastoma
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Combined anti-C1-INH and radiotherapy against glioblastoma. / Liljedahl, Emma; Konradsson, Elise; Gustafsson, Emma; Jonsson, Karolina Förnvik; Olofsson, Jill K.; Osther, Kurt; Ceberg, Crister; Redebrandt, Henrietta Nittby.
In: BMC Cancer, Vol. 23, 106, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Combined anti-C1-INH and radiotherapy against glioblastoma
AU - Liljedahl, Emma
AU - Konradsson, Elise
AU - Gustafsson, Emma
AU - Jonsson, Karolina Förnvik
AU - Olofsson, Jill K.
AU - Osther, Kurt
AU - Ceberg, Crister
AU - Redebrandt, Henrietta Nittby
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Complement system
KW - Glioblastoma
KW - Radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=85147124539&partnerID=8YFLogxK
U2 - 10.1186/s12885-023-10583-1
DO - 10.1186/s12885-023-10583-1
M3 - Journal article
C2 - 36717781
AN - SCOPUS:85147124539
VL - 23
JO - B M C Cancer
JF - B M C Cancer
SN - 1471-2407
M1 - 106
ER -
ID: 342093750