REDUCED TUMORIGENICITY OF HUMAN GASTRIC-CARCINOMA CELLS ENGINEERED TOPRODUCE IL-2 IN SCID MICE RECONSTITUTED WITH PERIPHERAL-BLOOD CELLS FROM CANCER-PATIENTS

We have examined the validity of a humanized immune system with an ani mal model to assess cytokine gene therapy for cancer patients. For tha t purpose, we prepared hematologically-reconstituted severe combined i mmunodeficiency mice by transferring patient's peripheral blood cells containing CD34(+) cells. These animals were inoculated subcutaneously with human gastric cancer lines transduced with cytokine genes. Tumor igenicity of interleukin-2-producing cells was significantly reduced i n reconstituted but not in non-reconstituted mice, whereas that of wil d-type and interleukin-6 producer cells was not affected irrespective of the reconstitution status. An inability to induce protective immuni ty in the reconstituted mice, which had rejected interleukin-2-produce rs, suggested that the effector cells mediating the antitumor response were non-T cells of donor origin. The experimental system presented i n this study seems to be a feasible model to investigate applicable cy tokines for patients. (C) 1998 Elsevier Science Ireland Ltd.