Advanced

Synergism between GM-CSF and IFNgamma: Enhanced immunotherapy in mice with glioma.

Smith, Karin E; Janelidze, Shorena LU ; Visse, Edward LU ; Badn, Wiaam LU ; Salford, Leif LU ; Siesjö, Peter LU and Darabi, Anna LU (2007) In International Journal of Cancer 120(1). p.75-80
Abstract
Glioblastoma multiforme is the most common malignant primary brain tumor and also one of the most therapy-resistant tumors. Because of the dismal prognosis, various therapies modulating the immune system have been developed in experimental models. Previously, we have shown a 37-70% cure in a rat glioma model where rats were peripherally immunized with tumor cells producing IFN. On the basis of these results, we wanted to investigate whether a combination of GM-CSF and IFN could improve the therapeutic effect in a mouse glioma model, GL261 (GL-wt). Three biweekly intraperitoneal (i.p.) immunizations with irradiated GM-CSF-transduced GL261 cells (GL-GM) induced a 44% survival in mice with intracranial glioma. While treatment of GL-wt and... (More)
Glioblastoma multiforme is the most common malignant primary brain tumor and also one of the most therapy-resistant tumors. Because of the dismal prognosis, various therapies modulating the immune system have been developed in experimental models. Previously, we have shown a 37-70% cure in a rat glioma model where rats were peripherally immunized with tumor cells producing IFN. On the basis of these results, we wanted to investigate whether a combination of GM-CSF and IFN could improve the therapeutic effect in a mouse glioma model, GL261 (GL-wt). Three biweekly intraperitoneal (i.p.) immunizations with irradiated GM-CSF-transduced GL261 cells (GL-GM) induced a 44% survival in mice with intracranial glioma. While treatment of GL-wt and GL-GM with IFN in vitro induced upregulation of MHC I and MHC II on the tumor cells, it could not enhance survival after immunization. However, immunizations with GL-GM combined with recombinant IFN at the immunization site synergistically enhanced survival with a cure rate of 88%. Tumors from mice receiving only 1 immunization on Day 10 after tumor inoculation were sectioned on Day 20 for analysis of leukocyte infiltration. Tumor volume was reduced and the infiltration of macrophages was denser in mice immunized with GL-GM combined with IFN compared with that of both wildtype and nonimmunized mice. To our knowledge, this is the first study to demonstrate a synergy between GM-CSF and IFN in experimental immunotherapy of tumors, by substantially increasing survival as well as inducing a potent anti-tumor response after only 1 postponed immunization. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
120
issue
1
pages
75 - 80
publisher
John Wiley & Sons
external identifiers
  • wos:000242653300011
  • scopus:33845422478
ISSN
0020-7136
DOI
10.1002/ijc.22286
language
English
LU publication?
yes
id
c4f03cd6-5469-48f2-b090-793780475ecf (old id 162312)
date added to LUP
2007-07-17 09:44:52
date last changed
2017-07-09 03:41:38
@article{c4f03cd6-5469-48f2-b090-793780475ecf,
  abstract     = {Glioblastoma multiforme is the most common malignant primary brain tumor and also one of the most therapy-resistant tumors. Because of the dismal prognosis, various therapies modulating the immune system have been developed in experimental models. Previously, we have shown a 37-70% cure in a rat glioma model where rats were peripherally immunized with tumor cells producing IFN. On the basis of these results, we wanted to investigate whether a combination of GM-CSF and IFN could improve the therapeutic effect in a mouse glioma model, GL261 (GL-wt). Three biweekly intraperitoneal (i.p.) immunizations with irradiated GM-CSF-transduced GL261 cells (GL-GM) induced a 44% survival in mice with intracranial glioma. While treatment of GL-wt and GL-GM with IFN in vitro induced upregulation of MHC I and MHC II on the tumor cells, it could not enhance survival after immunization. However, immunizations with GL-GM combined with recombinant IFN at the immunization site synergistically enhanced survival with a cure rate of 88%. Tumors from mice receiving only 1 immunization on Day 10 after tumor inoculation were sectioned on Day 20 for analysis of leukocyte infiltration. Tumor volume was reduced and the infiltration of macrophages was denser in mice immunized with GL-GM combined with IFN compared with that of both wildtype and nonimmunized mice. To our knowledge, this is the first study to demonstrate a synergy between GM-CSF and IFN in experimental immunotherapy of tumors, by substantially increasing survival as well as inducing a potent anti-tumor response after only 1 postponed immunization.},
  author       = {Smith, Karin E and Janelidze, Shorena and Visse, Edward and Badn, Wiaam and Salford, Leif and Siesjö, Peter and Darabi, Anna},
  issn         = {0020-7136},
  language     = {eng},
  number       = {1},
  pages        = {75--80},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Synergism between GM-CSF and IFNgamma: Enhanced immunotherapy in mice with glioma.},
  url          = {http://dx.doi.org/10.1002/ijc.22286},
  volume       = {120},
  year         = {2007},
}