Granulocyte-macrophage colony-stimulating factor gene transfer to dendritic cells or epidermal cells augments their antigen-presenting function including induction of anti-tumor immunity

Dendritic antigen-presenting cells derived from epidermis (Langerhans cells ), bone marrow, and peripheral blood can present a wide variety of antigens , including tumor-associated antigens, for various immune responses. The de velopment and function of dendritic cells is dependent upon a number of cyt okines including granulocyte-macrophage-colony-stimulating factor. For exam ple, Langerhans cells can present tumor-associated antigens for the inducti on of substantial in vivo anti-tumor immunity but only after activation in vitro by granulocyte-macrophage-colony-stimulating factor. Thus, we reasone d that insertion of a cDNA for granulocyte-macrophage-colony-stimulating fa ctor into dendritic antigen-presenting cells may allow for autocrine stimul ation and increased antigen-presenting capability. To test this possibility , we utilized an adenovirus vector to insert a cDNA for murine granulocyte- macrophage-colony-stimulating factor into the dendritic cell lines XS52-4D and XS106 (derived from neonatal mouse epidermis), bone marrow-derived dend ritic cells, and epidermal cells that contain Langerhans cells. Infection o f each of these cell types resulted in release of abundant quantities of gr anulocyte-macrophage-colony-stimulating factor. XS52-4D and XS106 cells inf ected with adenovirus granulocyte-macrophage-colony-stimulating factor exhi bited prolonged dendrites and greater expression of major histocompatibilit y complex class II molecules and CD86 compared with cells infected with a n ull vector. Granulocyte-macrophage-colony-stimulating factor cDNA-containin g XS cells, bone marrow-derived dendritic cells, and epidermal cells had mo re potent alloantigen presenting capability than cells infected with a null vector. Most importantly, granulocyte-macrophage-colony-stimulating factor gene-transferred epidermal cells were able to present tumor-associated ant igens for in vivo anti-tumor immunity against challenge with the S1509a spi ndle-cell tumor whereas null vector-infected cells were unable to prime for immunity, These results suggest that introduction of a cDNA for granulocyt e-macrophage-colony-stimulating factor into dendritic cells may be an effec tive means to augment their antigen-presenting capability and that granuloc yte-macrophage-colony-stimulating factor gene-transferred epidermal cells m ay be useful in tumor vaccination strategies.