Induction of specific anti-tumour immunity by interferon-gamma gene-transferred murine bladder carcinoma MBT-2.
Tumour cell-targeted cytokine gene therapy of cancer has been proposed using various cytokine genes including interferon (IFN)-gamma gene. In the course of the experimental approach using IFN-gamma gene, we established two IFN-gamma gene-transferred clonal sublines, IFN-gamma producer and non-producer, from a murine bladder tumour line MBT-2 via retroviral transfer of mouse IFN-gamma cDNA, and studied the influence of local secretion of IFN-gamma on tumour progression. While cell growth in vitro was not affected by gene transfer, expression of major histocompatibility complex (MHC) class I antigens was increased in both sublines. The IFN-gamma producing cells injected subcutaneously into syngeneic mice could not induce tumours but the non-producing cells tended to induce tumours. Thus the increase in MHC class I expression was not enough to cause tumour regression, and IFN-gamma secretion over a certain amount was needed for tumour suppression, probably in addition to MHC class I expression. Mice that rejected IFN-gamma producers established a specific anti-tumour immunity and spleen cells derived from the mice contained populations of CD8+ effector T cells against MBT-2 cells. These results supported previous reports that IFN-gamma gene transfer into tumour cells apparently abrogated the tumorigenicity by augmenting the host anti-tumour immunity, and were encouraging for a promising execution of the tumour cell-targeted IFN-gamma gene therapy against human bladder cancers.
Department of Urology, Faculty of Medicine, Kyoto University.
M
M
Hiura
T
T
Hashimura
Y
Y
Watanabe
K
K
Kuribayashi
O
O
Yoshida
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007109:Immunity; D007371:Interferon-gamma / Q000235:genetics* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D014162:Transfection; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*
D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma