LOSS OF TUMORIGENICITY OF HUMAN PANCREATIC-CARCINOMA CELLS ENGINEEREDTO PRODUCE INTERLEUKIN-2 OR INTERLEUKIN-4 IN NUDE-MICE - A POTENTIALITY FOR CANCER GENE-THERAPY

To examine the possibility of cytokine gene therapy in relation to pan creatic cancer, we evaluated the antitumor effect of human pancreatic carcinoma cells (AsPC-1) which were retrovirally-transduced with sever al kinds of cytokine genes. These cells were inoculated into BALB/c nu de mice and their tumor volumes were assessed. The in vitro growth rat e of the transduced cells was not different from that of a parental ce ll line. Among the transduced cells, human interleukin (IL)-6-transduc ed AsPC-1 and mouse granulocyte macrophage colony-stimulating factor-t ransduced AsPC-1 cells showed a significant retardation of tumor growt h compared with a parental cell line. In the cases of AsPC-1 cells tra nsduced with the human IL-2 or mouse IL-4 gene, small tumors were gene rated but thereafter they regressed completely. Histological examinati ons showed monocytic cell infiltration around the tumors of IL-2- or I L-4-producing cells. These data suggest that secretion of IL-2 or IL-4 from tumor cells can induce an antitumor effect even in the defective condition of mature T cells. (C) 1998 Elsevier Science Ireland Ltd.