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Immunotherapy against malignant brain tumors - of mice and men

Enell Smith, Karin LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:56.
Abstract
Glioblastoma Multiforme (GBM) is the most abundant and most aggressive primary brain tumor in adults. Due to the infiltrative growth of the tumor, surgery will never be radical. Radiation and chemotherapy only marginally improve the poor prognosis due to the ability of the GBM to develop resistance towards these treatments. Therefore it is of great importance to find new efficient treatment modalities.

The aim with this thesis was to develop and evaluate a cytokine based immunotherapy as treatment for GBM in both an experimental mouse glioma model as well as in patients suffering from GBM.

In paper I we demonstrate the establishment of a GM-CSF and IFNγ based immunotherapy in the mouse glioma model, GL261. Mice with... (More)
Glioblastoma Multiforme (GBM) is the most abundant and most aggressive primary brain tumor in adults. Due to the infiltrative growth of the tumor, surgery will never be radical. Radiation and chemotherapy only marginally improve the poor prognosis due to the ability of the GBM to develop resistance towards these treatments. Therefore it is of great importance to find new efficient treatment modalities.

The aim with this thesis was to develop and evaluate a cytokine based immunotherapy as treatment for GBM in both an experimental mouse glioma model as well as in patients suffering from GBM.

In paper I we demonstrate the establishment of a GM-CSF and IFNγ based immunotherapy in the mouse glioma model, GL261. Mice with intracranial gliomas were immunized intraperitoneally with GL261 cell genetically modified to produce GM-CSF combined with recombinant IFNγ. This combination synergistically enhanced survival to 90%. In paper II-III we investigated the immune responses elicited by these immunizations both systemically as well as locally in the tumor. We found that the immunizations with GM-CSF and IFNγ were highly dependent on T-cells for mediating survival of the mice. In paper IV we monitored the immune responses elicited in GBM patients receiving IFNγ based immunotherapy using ELIspot and CBA.

Immunotherapy enhances the patient’s own antitumoral immune responses otherwise suppressed by the tumor. We believe that this treatment, in combination with conventional treatments such as surgery,

radiotherapy and chemotherapy, has a great promise for the future treatment of patients with GBM. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof. agrégé sous octroi Vallieres, Luc, Université Laval, Quebec, Canada
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Tumor Immunology, Immunotherapy, Glioma, Mouse
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:56
pages
112 pages
publisher
Department of Clinical Sciences, Lund University
defense location
Segerfalkssalen, BMC A10
defense date
2008-05-24 09:15
ISSN
1652-8220
ISBN
978-91-86059-09-5
language
English
LU publication?
yes
id
9af6292f-3c03-498b-a905-77a564fb834e (old id 1145924)
date added to LUP
2008-04-28 13:23:16
date last changed
2016-09-19 08:44:45
@phdthesis{9af6292f-3c03-498b-a905-77a564fb834e,
  abstract     = {Glioblastoma Multiforme (GBM) is the most abundant and most aggressive primary brain tumor in adults. Due to the infiltrative growth of the tumor, surgery will never be radical. Radiation and chemotherapy only marginally improve the poor prognosis due to the ability of the GBM to develop resistance towards these treatments. Therefore it is of great importance to find new efficient treatment modalities. <br/><br>
The aim with this thesis was to develop and evaluate a cytokine based immunotherapy as treatment for GBM in both an experimental mouse glioma model as well as in patients suffering from GBM.<br/><br>
In paper I we demonstrate the establishment of a GM-CSF and IFNγ based immunotherapy in the mouse glioma model, GL261. Mice with intracranial gliomas were immunized intraperitoneally with GL261 cell genetically modified to produce GM-CSF combined with recombinant IFNγ. This combination synergistically enhanced survival to 90%. In paper II-III we investigated the immune responses elicited by these immunizations both systemically as well as locally in the tumor. We found that the immunizations with GM-CSF and IFNγ were highly dependent on T-cells for mediating survival of the mice. In paper IV we monitored the immune responses elicited in GBM patients receiving IFNγ based immunotherapy using ELIspot and CBA.<br/><br>
Immunotherapy enhances the patient’s own antitumoral immune responses otherwise suppressed by the tumor. We believe that this treatment, in combination with conventional treatments such as surgery,<br/><br>
radiotherapy and chemotherapy, has a great promise for the future treatment of patients with GBM.},
  author       = {Enell Smith, Karin},
  isbn         = {978-91-86059-09-5},
  issn         = {1652-8220},
  keyword      = {Tumor Immunology,Immunotherapy,Glioma,Mouse},
  language     = {eng},
  pages        = {112},
  publisher    = {Department of Clinical Sciences, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Immunotherapy against malignant brain tumors - of mice and men},
  volume       = {2008:56},
  year         = {2008},
}