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Immunizations with IFNgamma secreting tumor cells can eliminate fully established and invasive rat gliomas.

Janelidze, Shorena LU ; Bexell, Daniel LU ; Badn, Wiaam LU ; Darabi, Anna LU ; Enell Smith, Karin LU ; Fritzell, Sara LU ; Gunnarsson, Salina LU ; Milos, Peter; Bengzon, Johan LU and Salford, Leif LU , et al. (2009) In Journal of Immunotherapy 32(6). p.593-601
Abstract
Immunotherapy of malignant primary brain tumors holds the potential to improve the dismal prognosis after current clinical therapy. Although immunotherapy of experimental gliomas has been demonstrated to have the capacity to cure intracerebral tumors no convincing effects of immunotherapy have been shown in clinical trials. One reason for this could be that some of the models used do not display full features of human glioblastomas. The N29 rat gliomas exhibited all the histologic features of human glioblastoma multiforme including nuclear atypia, mitotic figures, necrosis, and diffuse infiltration into the normal brain tissue. Surprisingly, immunotherapy with autologous interferon gamma producing tumor cells against preestablished... (More)
Immunotherapy of malignant primary brain tumors holds the potential to improve the dismal prognosis after current clinical therapy. Although immunotherapy of experimental gliomas has been demonstrated to have the capacity to cure intracerebral tumors no convincing effects of immunotherapy have been shown in clinical trials. One reason for this could be that some of the models used do not display full features of human glioblastomas. The N29 rat gliomas exhibited all the histologic features of human glioblastoma multiforme including nuclear atypia, mitotic figures, necrosis, and diffuse infiltration into the normal brain tissue. Surprisingly, immunotherapy with autologous interferon gamma producing tumor cells against preestablished intracerebral N29 tumors yielded a higher cure rate than immunotherapy against less invasive tumors. Furthermore, when immunizations were postponed until day 5 after tumor establishment 50% of the animals survived. When immunizations were postponed until day 11 after tumor establishment no glioma-bearing animals were cured but survival was significantly prolonged. The superior effect of immunotherapy in the invasive N29 model compared with the less invasive tumors could depend on combined effects of up-regulation of major histocompatibility complex I and induction of major histocompatibility complex II plus CD80 after transfection and irradiation of the tumor cells used for immunizations. This study demonstrates that immunotherapy against experimental brain tumors indeed is feasible even against highly invasive and established tumors. These results strengthen the translational potential of immunotherapy against malignant brain tumors. (Less)
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published
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Journal of Immunotherapy
volume
32
issue
6
pages
593 - 601
publisher
Lippincott Williams & Wilkins
external identifiers
  • PMID:19483650
  • Scopus:67651151521
ISSN
1524-9557
DOI
10.1097/CJI.0b013e3181a95148
language
English
LU publication?
yes
id
c2de6e5f-d8ad-46e9-8b38-3b5ca21e5bdf (old id 1434680)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19483650?dopt=Abstract
date added to LUP
2009-07-02 13:00:52
date last changed
2017-01-01 07:48:43
@article{c2de6e5f-d8ad-46e9-8b38-3b5ca21e5bdf,
  abstract     = {Immunotherapy of malignant primary brain tumors holds the potential to improve the dismal prognosis after current clinical therapy. Although immunotherapy of experimental gliomas has been demonstrated to have the capacity to cure intracerebral tumors no convincing effects of immunotherapy have been shown in clinical trials. One reason for this could be that some of the models used do not display full features of human glioblastomas. The N29 rat gliomas exhibited all the histologic features of human glioblastoma multiforme including nuclear atypia, mitotic figures, necrosis, and diffuse infiltration into the normal brain tissue. Surprisingly, immunotherapy with autologous interferon gamma producing tumor cells against preestablished intracerebral N29 tumors yielded a higher cure rate than immunotherapy against less invasive tumors. Furthermore, when immunizations were postponed until day 5 after tumor establishment 50% of the animals survived. When immunizations were postponed until day 11 after tumor establishment no glioma-bearing animals were cured but survival was significantly prolonged. The superior effect of immunotherapy in the invasive N29 model compared with the less invasive tumors could depend on combined effects of up-regulation of major histocompatibility complex I and induction of major histocompatibility complex II plus CD80 after transfection and irradiation of the tumor cells used for immunizations. This study demonstrates that immunotherapy against experimental brain tumors indeed is feasible even against highly invasive and established tumors. These results strengthen the translational potential of immunotherapy against malignant brain tumors.},
  author       = {Janelidze, Shorena and Bexell, Daniel and Badn, Wiaam and Darabi, Anna and Enell Smith, Karin and Fritzell, Sara and Gunnarsson, Salina and Milos, Peter and Bengzon, Johan and Salford, Leif and Siesjö, Peter and Visse, Edward},
  issn         = {1524-9557},
  language     = {eng},
  number       = {6},
  pages        = {593--601},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Immunotherapy},
  title        = {Immunizations with IFNgamma secreting tumor cells can eliminate fully established and invasive rat gliomas.},
  url          = {http://dx.doi.org/10.1097/CJI.0b013e3181a95148},
  volume       = {32},
  year         = {2009},
}