Induction of specific anti-tumour immunity by interferon-gamma gene-transferred murine bladder carcinoma MBT-2.

ABSTRACT

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.