MURINE SARCOMA-CELLS TRANSFECTED WITH INTERLEUKIN-12 ARE REJECTED IN-VIVO INDUCING PROTECTIVE AND CURATIVE IMMUNE-RESPONSES AGAINST THE PARENTAL CELLS

We evaluated the in vivo antitumor activity of interleukin 12 (IL-12) in a murine sarcoma model using gene transfer techniques. M-MSV-BALB/3 T3 clone engineered to secrete IL-12 was rejected when transplanted in to syngeneic BALB/c mice, The tumors rejected in vivo not only induced protective immunity against subcutaneous growth or pulmonary metastas es of the parental, nontransfected tumor cells, but also induced curat ive immunity against established subcutaneous tumors. A generation of CTL activity was significantly induced by injection of IL-12-secreting tumor cells, The wild-type and IL-12-secreting tumor cells grew equal ly well in nude mice, implying that T-lymphocytes could play a major r ole in mediating the antitumor effects of IL-12. Adoptive transfer exp eriments subsequently identified both CD4(+) and CD8(+) T-cells as the major mediators. It was also shown that tumor cells transiently expre ssing IL-12 were as potent as stable transformants in causing the anti tumor activity of IL-12. The results described in the present studies indicate that IL-12 secreted from tumor cells is a potent mediator in induction of protective as well as curative immune responses against t he parental cells in vivo.