TRANSDUCTION POTENTIAL OF HUMAN RETROVIRUSES IN HIGHLY PROLIFERATING SMALL-CELL LUNG-CANCER CELLS AS WELL AS NONPROLIFERATING HEMATOPOIETICSTEM-CELLS

Direct gene transfer to solid tissues or metastatic cancer cells requi res vectors capable of in vivo transduction to specific cells. The pre dominant retroviral vectors of murine origin are inactivated by human complement, which precludes their use in vivo. Such inactivation does not take place with vectors based on human retroviruses. Murine retrov iral vectors are also limited to proliferating cells, which human retr oviruses are not. In this study we examined whether or not a vector us ing components from the human retroviruses HIV-1 and HTLV-1 could infe ct small-cell lung cancer cells and resting CD34+ hematopoietic stem c ells. While HIV-1 itself was unable to infect cells lacking the CD4-me mbrane molecule, chimeric viral particles (pseudotype virus) with HIV- 1 genome and HTLV-1 envelope components were able to infect both CD4-c ontaining lymphocytic cells, CD4-negative tumour cells and hematopoiet ic stem cells. After infection with the pseudotype vector, the RNA gen ome was reverse transcribed and integrated. Transduction efficiency an d gene expression under the HIV-1 LTR promoter in both tumour and stem cells were found to be of a similar or greater magnitude than in lymp hocytic cells. These results suggest that gene transfer targeting prol iferating as well as resting cells in vivo may be realized using compo nents from human retroviruses.