Vaccination with tumor cell lysate-pulsed dendritic cells augments the effect of IFN-beta gene therapy for malignant glioma in an experimental mouse intracranial glioma.
Interferon-beta (IFN-beta) has been used as an antitumor drug against human glioma, melanoma and medulloblastoma since the 1980s. Recently, we developed a new gene therapy using the IFN-beta gene against malignant gliomas and then began clinical trials in 2000. Since stimulation of immune system was one mechanism of antitumor effect induced by IFN-beta gene therapy, we hypothesized that combination of IFN-beta gene therapy with immunotherapy might increase its effectiveness. In the present study, we tested whether combination therapy with IFN-beta gene therapy and immunotherapy using tumor cell lysate-pulsed dendritic cells (DCs) would increase the efficacy of IFN-beta gene therapy. In an experimental mouse intracranial glioma (GL261), which cannot be cured by either IFN-beta gene therapy or DC immunotherapy alone, IFN-beta gene therapy following DC immunotherapy resulted in a significant prolongation in survival of the mice. Moreover, when this combination was performed twice, 50% of treated mice survived longer than 100 days. Considering these results, this combination therapy may be one promising candidate for glioma therapy in the near future.
Saito
Ryuta
R
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mizuno
Masaaki
M
Nakahara
Norimoto
N
Tsuno
Takaya
T
Kumabe
Toshihiro
T
Yoshimoto
Takashi
T
Yoshida
Jun
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000662:veterinary; D019496:Cancer Vaccines; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics* / Q000628:therapy* / Q000662:veterinary; D007167:Immunotherapy; D016899:Interferon-beta / Q000235:genetics* / Q000494:pharmacology*; D008055:Lipids; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D010957:Plasmids; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D008055:Lipids; D016899:Interferon-beta