THE INDUCTION OF IMMUNE-RESPONSES TO MURINE MALIGNANT MESOTHELIOMA BYIL-2 GENE-TRANSFER

Stable IL-2 transfectant clones have been derived from two non-immunog enic murine malignant mesothelioma (MM) cell lines to investigate the induction of protective antitumour immunity to MM, AC29-IL-2 transfect ant clones grew at a slower rate in vivo than the parental cell Line o r a transfectant control clone but all inoculated mice developed tumou rs 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 r ejected the AB1-IL-2 transfectants were challenged with parental AB1 c ells, a proportion (16-70%) of mice from each group remained tumour fr ee at least 45 days after challenge (naive mice developed rumours with in 26 days). The inhibition of growth of the initial inoculum of AB1-I L-2 transfectants was independent of CD4(+) and CD8(+) cells, consiste nt with the demonstration of non-specific cytotoxic activity by spleno cytes from mice inoculated with the IL-2 transfectants. These data sug gest 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 b e subject to downregulation 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 gene ration of protective immunity to MM.