TRANSFECTION OF THE GENE FOR B7-1 BUT NOT B7-2 CAN INDUCE IMMUNITY TOMURINE MALIGNANT MESOTHELIOMA

Transfection of the genes encoding the co-stimulatory molecules B7-1 a nd B7-2 has enhanced the development of immunity to a variety of exper imental tumors, although most of these were inherently immunogenic. We have determined the effect of expression of these genes on the induct ion of immunity to 2 non-immunogenic murine malignant mesothelioma (MM ) cell lines (AC29 and AB1). We had previously shown that B7-1 transfe ction into AC29 delayed but did not prevent tumor development by certa in of the transfectant clones. Here we demonstrate that over-expressio n of B7-1 can inhibit tumor development by certain AB1-B7-1 clones, th at inhibition of transfectant growth is dependent on CD4(+) and CD8(+) T cells and that mice that reject some of these transfectant clones a re capable of rejecting subsequent inocula of the parental cell line, AB1. The transfectant clones can generate tumor-specific cytotoxic T c ells, By contrast, expression of B7-2 in several clones derived from e ither AB1 or AC29 had no significant effect on the development of tumo rs in vivo. Our data are consistent with data from other systems that show differences in the effect of modification by B7-1 or B7-2 on the modulation of anti-tumor immune responses. They demonstrate that such modifications can induce protective immunity against an MM cell line b ut confirm the intra- and inter-tumoral heterogeneity in the effect of genetic modification on the induction of immunity. Our observations a re relevant to human MM because these cell lines have been derived fro m asbestos-induced tumors and share many properties with human cell li nes of the same histological type. (C) 1997 Wiley-Liss, Inc.