ADENOVIRAL VECTORS EFFICIENTLY TARGET-CELL LINES DERIVED FROM SELECTED LYMPHOCYTIC MALIGNANCIES, INCLUDING ANAPLASTIC LARGE-CELL LYMPHOMA AND HODGKINS-DISEASE

We have hypothesized that adenoviral vectors might mediate gene transf er into cell lines derived from human lymphocytic malignancies, such a s lymphoma, lymphocytic leukemia, and myeloma, A panel of 33 cell line s was studied for their ability to be transduced by an adenoviral (AD) vector encoding the Escherichia coli beta-galactosidase gene (AD-beta gal). A cytochemical assay and a flow cytometry assay both demonstrat ed that a subset of lymphocytic cell lines can be efficiently transduc ed by adenoviral vectors. In particular, three: of three anaplastic la rge cell lymphoma lines, two of two Hodgkin's disease cell lines, two of seven Burkitt's lymphoma cell lines, and three of five myeloma cell lines exhibited efficient gene transfer. The ability of an AD vector expressing the thymidine kinase (tk) gene from herpes simplex virus-1 (AD-tk) followed by ganciclovir (GCV) to kill 11 of these lymphocytic cell lines was studied, In eight of the cell lines tested, more than 6 8% of the cells were killed by AD-tk/GCV. Similar results were obtaine d using an adenoviral vector expressing the wildtype p53 tumor suppres sor gene (AD-p53). Thus, AD-tk/GCV and AD-p53 both demonstrated effici ent killing of these cell lines. These data document that adenoviral v ectors are valuable reagents for the introduction of genes into select ed lymphocytic cell lines. These data also suggest that adenoviral vec tors might be useful for gene therapy of subsets of lymphocytic malign ancy.