The induction of immune responses to murine malignant mesothelioma by IL-2 gene transfer.

Abstract

Stable IL-2 transfectant clones have been derived from two non-immunogenic murine malignant mesothelioma (MM) cell lines to investigate the induction of protective antitumor immunity to MM. AC29-IL-2 transfectant clones grew at a slower rate in vivo than the parental cell line or a transfectant control clone but all inoculated mice developed tumours despite the continued ability of the tumour cells to express IL-2. Tumour development after inoculation of AB1-IL-2 transfectants varied, the degree of in vivo inhibition (40-100%) being directly related to the rate of IL-2 secretion of the transfectants. When mice which had rejected the AB1-IL-2 transfectants were challenged with parental AB1 cells, a proportion (16-70%) of mice from each group remained tumour free at least 45 days after challenge (naive mice developed tumours within 26 days). The inhibition of growth of the initial inoculum of AB1-IL-2 transfectants was independent of CD4+ and CD8+ cells, consistent with the demonstration of non-specific cytotoxic activity by splenocytes from mice inoculated with the IL-2 transfectants. These data suggest that IL-2 expression by MM cells is capable of generating in vivo immunity to the tumour. This immunity may be relatively weak or may be subject to down-regulation so that consistent rejection of unmodified tumour cells is not achieved. Genetic modification with combinations of genes, including IL-2 and B7-1, will be necessary for reliable generation of protective immunity to MM.