GENETICALLY-MODIFIED TUMOR VACCINES - INSERTION OF THE IL-2 GENE DOWN-REGULATES TUMORIGENICITY MORE EFFICIENTLY THAN INSERTION OF THE CD80 GENE

Two genes, the gene coding for IL-2 and the gene encoding the CD80 mol ecule, were inserted into murine sarcoma MC12 cells. Tumorigenicity of a variety of cell clones with different expression of the inserted ge nes was assessed. Most of the genetically manipulated MC12 cell clones were less tumorigenic than the parental MC12 cell population. Tumorig enicity of the clones declined with increasing production of IL-2 as w ell as with the increasing expression of the CD80 molecule. When the t umorigenicity of the clones carrying an inserted IL-2 gene was compare d with that of the clones carrying an inserted CD80 gene, it was found that the insertion of the IL-2 gene suppresses tumorigenicity more ef ficiently than insertion of the CD80 gene. Admixture of the IL-2-produ cing MC12 clones to the tumorigenic CD80(+) MC12 cell doses could comp letely inhibit the tumorigenicity of the CD80(+) cells. Insertion of t he CD80 gene into sarcoma cells substantially enhanced the adhesive in teraction between the MC12 sarcoma and syngeneic T lymphocytes.