TRANSDUCTION OF GENES-CODING FOR A HISTOCOMPATIBILITY (MHC) ANTIGEN AND FOR ITS PHYSIOLOGICAL INDUCER INTERFERON-GAMMA IN THE SAME CELL - EFFICIENT MHC EXPRESSION AND INHIBITION OF TUMOR AND METASTASIS GROWTH

The mouse mammary carcinoma TS/A, of BALB/c (H-2(d)) origin, was trans fected with the murine interferon-gamma (IFN-gamma) gene (Int. J. Canc er 55: 320, 1993). We used IFN-gamma transfectants as recipients for a second round of transfections with murine allogeneic class I histocom patibility (H-2(b)) genes that are modulated by IFN. Transfectants wit h either gene alone, as well as parent TS/A cells (TS/A-pc), were used as controls. Only double transfectants expressed high levels of the a llogeneic H-2(b) genes, while in H-2(b) single transfectants the expre ssion was very low (but was induced by treatment with exogenous IFN-ga mma). The tumorigenic potential of IFN-gamma or H-2(b) single transfec tants was reduced in comparison to TS/A-pc. IFN-gamma + H-2K(b) double transfectants were almost nontumorigenic, while IFN-gamma + H-2D(b) c lones gave rise to tumors in about one-half of mice, The experimental metastatic ability of all IFN-gamma + H-2(b) double transfectants was very low. IFN-gamma single transfectants were known to induce a strong macrophage response in the host. The expression of allogeneic H-2 ant igens added a T-lymphocyte-mediated response that accounted for the lo wer tumorigenicity of double transfectants. These results show that it is possible to steer the immune response evoked by tumor cells for th erapeutic purposes, Moreover, the high H-2 expression obtained in IFN- gamma + H-2(b) double transfectants suggests that single IFN-gamma tra nsfectants are ideal recipients for all IFN-sensitive genes. This appr oach can be used also for other general-purpose inducers of gene expre ssion.