title: Glioma-specific cytotoxic T cells can be effectively induced by subcutaneous vaccination of irradiated wild-type tumor cells without artificial cytokine production.
abstract: Effective induction of systemic antitumor immunity is a crucial step for success of immune gene therapy for intracerebral gliomas. We examined in this study the ability to induce glioma-specific cytotoxic T lymphocytes (CTL) by subcutaneous (s.c.) immunization of irradiated whole-tumor cell vaccine with or without artificial cytokine production, and also examined in vivo efficacy of the induced CTL against a rat brain tumor model with 9L gliosarcoma cells. Murine neuroblastoma C1300 cells transduced with the interleukin-2 (IL-2), IL-4 or granulocyte-macrophage colony-stimulating factor (GM-CSF) gene (C1300/IL-2, C1300/IL-4 or C1300/GM-CSF) were used as cytokine-producers. Glioma-specific CTL activity was equivalently induced in the rats vaccinated s.c. with irradiated 9L, irradiated IL-2-producing 9L cells or the mixed population of irradiated 9L and C1300/IL-2 cells, while the activity was relatively lower in the rats vaccinated with irradiated 9L cells mixed with either C1300/IL-4 or C1300/GM-CSF cells. In the rats immunized s.c. with irradiated 9L cells, intracerebral (i.c.) 9L tumors implanted together with either C1300/IL-2 or C1300/IL-4 were completely rejected. Pre-established brain tumor also could be eliminated by the s.c. immunization of irradiated 9L cells and i.c. transplantation of IL-2-producers. These results suggest that glioma-specific CTLs could be effectively induced by s.c. immunization of irradiated wild-type tumor cells without artificial cytokine production.
authors.affiliation: Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan. iwadate@med.m.chiba-u.ac.jp
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwadate
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakiyama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sato
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015316:Genetic Therapy; D005910:Glioma / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D007114:Immunization; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000528:radiation effects
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor