IMPROVED IMMUNOSTIMULATORY FUNCTION OF BONE-MARROW-DERIVED MACROPHAGES TRANSDUCED WITH THE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTORGENE

Professional antigen presenting cells (APCs) play a prominent role in generation of antitumor immunity. Granulocyte macrophage colony stimul ator factor (GM-CSF) has been shown to increase antigen presenting cap acity of macrophages and dendritic cells. We examined whether retrovir al mediated gene transfer of the murine GM-CSF cDNA into bone marrow p recursor cells would result in generation of mature APCs with improved immunostimulatory function. We show that murine bone marrow cells can be stably transduced to produce GM-CSF (200-300 pg/mL per 10(6) cells in 24 hours). These cells proliferated in the absence of exogenous gr owth factor for 25 days and expressed the macrophage markers Mac-1, Ma c-3 and F4/80. GM-CSF transduced bone marrow cells had enhanced stimul atory capacity in a primary mixed lymphocyte-APC reaction and improved antigen presenting function in a T helper clone proliferation assay. These data demonstrate that bone marrow cells can be genetically engin eered to secrete GM-CSF resulting in expansion of effective APCs. GM-C SF transduced APCs may be used as natural adjuvants in stimulating imm une responses in vivo.