Improved immunostimulatory function of bone marrow derived macrophages transduced with the granulocyte-macrophage...

Professional antigen presenting cells (APCs) play a prominent role in generation of antitumor immunity. Granulocyte macrophage colony stimulator factor (GM-CSF) has been shown to increase antigen presenting capacity of macrophages and dendritic cells. We examined whether retroviral mediated gene transfer of the murine GM-CSF cDNA into bone marrow precursor 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 growth factor for 25 days and expressed the macrophage markers Mac-1, Mac-3 and F4/80. GM-CSF transduced bone marrow cells had enhanced stimulatory 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 engineered to secrete GM-CSF resulting in expansion of effective APCs. GM-CSF transduced APCs may be used as natural adjuvants in stimulating immune responses in vivo.