BROADENED CLINICAL UTILITY OF GENE GUN-MEDIATED, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR CDNA-BASED TUMOR-CELL VACCINES AS DEMONSTRATED WITH A MOUSE MYELOMA MODEL

Effective immunization against the murine B16 melanoma by a nonviral a pproach in which a gene gun is used to transfer GM-CSF cDNA into tumor cells has been described. We have extended this nonviral approach by using the poorly immunogenic murine myeloma MPC11 model, Vaccination w ith the transfected, GM-CSF-expressing MPC11 cells induced a potent an titumor cytotoxic T lymphocyte response associated with tumor rejectio n in the majority of the test mice, Furthermore, nearly 100% (27 of 28 ) of the tumor-free mice were able to reject a tumor rechallenge. Whil e this approach is clinically attractive because of minimal tissue man ipulation/culturing and the absence of infectious agents, a number of tested human primary tumors, including myeloma cells, have failed to p roduce high levels of GM-CSF after gene gun transfection, To circumven t the low transfection efficiency in certain human tumor cells, we sho wed that combining irradiated tumor cells to provide tumor antigens to gether with gene gun-transfected fibroblasts to provide GM-CSF induced effective tumor rejection. We also report that normal human skin fibr oblasts transfected by the gene gun produce high levels of human GM-CS F (250 ng/10(6) cells/24 hr), These results suggest that combining irr adiated tumor cells with gene gun-transfected fibroblasts results in a ntitumor immune responses and may allow for a wider application of thi s approach to cancer immunotherapy.