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

Javier García-Castro, José Carlos Segovia, Félix García-Sánchez, Rosa Lillo, Jesús Gómez-Navarro, David T. Curiel, Juan A. Bueren

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16 Scopus citations

Abstract

On the basis of the susceptibility of normal myelomonocytic cells to adenoviral vectors, we have studied the possibility of selectively transducing myelomonocytic murine leukemic cells (WEHI-3B) with regular (Reg-Ad) and genetically modified (RGD-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 infection, 20-30% of mouse bone marrow (BM) cells were positive for the transgene. When RGD-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 cells to become positive for the marker transgene (EGFP). Under these conditions, 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 BM 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 transduction of WEHI-3B cells with Reg-Ad, suggesting that the abrogation of this requirement accounts for the improved infectivity of these leukemic cells and for the selectivity of RGD-Ad in targeting WEHI-3B leukemia cells.

Original languageEnglish
Pages (from-to)70-77
Number of pages8
JournalMolecular Therapy
Volume3
Issue number1
DOIs
StatePublished - 2001

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