Effective induction of antiglioma cytotoxic T cells by coadministration of interferon-beta gene vector and dendritic cells.
As type I interferons (IFNs) enhance the stimulatory activity of dendritic cells (DCs), we hypothesized that transfection of glioma cells with the IFN-beta gene in the presence of DCs would provide particularly effective antitumor activity by both facilitating apoptosis of glioma cells and presenting the resulting glioma antigens to T cell by DCs, thereby inducing specific T-cell responses against glioma cells. A mouse glioma cell line 203G was first transfected with cDNA encoding IFN-beta using cationic liposomes, then cocultured with syngeneic bone marrow-derived DCs and naïve splenic T cells. The 203G cells were almost completely killed following 96-hour coculture with DCs and T cells, and strong tumor-specific cytotoxic T-lymphocyte (CTL) activity accompanied by high level interleukin (IL)-12 and IFN-gamma production was observed in culture. In addition, omission of either IFN-beta gene delivery, DCs or T cells from the coculture completely abrogated the induction of the CTL activity, suggesting that the combination of these components was required to elicit an optimal effect. On the basis of these in vitro data, syngeneic animals bearing subcutaneous 203G tumors received intratumoral injections of IFN-beta gene and DCs. Suppression of the tumor growth by this combinational therapy was superior to treatment with DC or IFN-beta gene solely. This combination may constitute a new therapeutic strategy to induce potent antiglioma immune responses.
Nakahara
Norimoto
N
Department of Bio-Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Pollack
Ian F
IF
Storkus
Walter J
WJ
Wakabayashi
Toshihiko
T
Yoshida
Jun
J
Okada
Hideho
H
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D004337:Drug Carriers; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D005910:Glioma / Q000276:immunology* / Q000473:pathology; D016899:Interferon-beta / Q000008:administration & dosage / Q000235:genetics*; D008081:Liposomes; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D008081:Liposomes; D016899:Interferon-beta