Reduced tumorigenicity of human gastric carcinoma cells engineered to produce 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 animal model to assess cytokine gene therapy for cancer patients. For that purpose, we prepared hematologically-reconstituted severe combined immunodeficiency mice by transferring patientʹs peripheral blood cells containing CD34+ cells. These animals were inoculated subcutaneously with human gastric cancer lines transduced with cytokine genes. Tumorigenicity of interleukin-2-producing cells was significantly reduced in reconstituted but not in non-reconstituted mice, whereas that of wild-type and interleukin-6 producer cells was not affected irrespective of the reconstitution status. An inability to induce protective immunity in the reconstituted mice, which had rejected interleukin-2-producers, suggested that the effector cells mediating the antitumor response were non-T cells of donor origin. The experimental system presented in this study seems to be a feasible model to investigate applicable cytokines for patients.