Immunizations with IFNgamma secreting tumor cells can eliminate fully established and invasive rat gliomas.
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.
Janelidze
Shorena
S
Glioma Immunotherapy Group, Lund University, Lund, Sweden.
Bexell
Daniel
D
Badn
Wiaam
W
Darabi
Anna
A
Smith
Karin-Enell
KE
Fritzell
Sara
S
Gunnarsson
Salina
S
Milos
Peter
P
Bengzon
Johan
J
Salford
Leif Göran
LG
Siesjö
Peter
P
Visse
Edward
E
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D018122:B7-1 Antigen; D007371:Interferon-gamma