Selective transduction of murine myelomonocytic leukemia cells (WEHI-3B) with regular and RGD-adenoviral vectors

On the basis of the susceptibility of normal myelomonocytic cells to adenov iral vectors, we have studied the possibility of selectively transducing my elomonocytic murine leukemic cells (WEHI-3B) with regular (Reg-Ad) and gene tically modified (RCD-Ad) adenoviral vectors. An 8-h incubation of WEHI-3B cells with 100 pfu of Reg-Ad vectors/cell resulted in the whole population becoming positive for transgene expression. Under identical conditions of i nfection, 20-30% of mouse bone marrow (BM) cells were positive for the tran sgene. When RCD-Ad vectors were used, a brief exposure (10 min) of WEHI-3B cells to 150 pfu of the virus/cell was enough for 100% of the leukemia cell s to become positive for the marker transgene (EGFP). Under these condition s, only 15-20% of BM cells and of primitive hematopoietic progenitors (Lin( -)Sca-(1+) cells) became EGFP(+), indicating an improved selectivity of the vectors for the leukemic cells. The incubation of WEHI-3B but not normal B M cells with soluble fiber protein (FP) inhibited the infection with Reg-Ad . The use of the RGD-Ad bypassed the FP-CAR interaction required for the tr ansduction of WEHI-3B cells with Reg-Ad, suggesting that the abrogation of this requirement accounts for the improved infectivity of these leukemic ce lls and for the selectivity of RCD-Ad in targeting WEHI-3B leukemia cells.