Adenoviral vectors efficiently target cell lines derived from selected lymphocytic malignancies, including anaplastic large cell lymphoma and Hodgkin's disease.
We have hypothesized that adenoviral vectors might mediate gene transfer into cell lines derived from human lymphocytic malignancies, such as lymphoma, lymphocytic leukemia, and myeloma. A panel of 33 cell lines was studied for their ability to be transduced by an adenoviral (AD) vector encoding the Escherichia coli beta-galactosidase gene (AD-betagal). A cytochemical assay and a flow cytometry assay both demonstrated that a subset of lymphocytic cell lines can be efficiently transduced by adenoviral vectors. In particular, three of three anaplastic large 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 68% of the cells were killed by AD-tk/GCV. Similar results were obtained using an adenoviral vector expressing the wild-type p53 tumor suppressor gene (AD-p53). Thus, AD-tk/GCV and AD-p53 both demonstrated efficient killing of these cell lines. These data document that adenoviral vectors are valuable reagents for the introduction of genes into selected lymphocytic cell lines. These data also suggest that adenoviral vectors might be useful for gene therapy of subsets of lymphocytic malignancy.
Meeker
T C
TC
Departments of Medicine and Biochemistry and the Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536, USA.
Lay
L T
LT
Wroblewski
J M
JM
Turturro
F
F
Li
Z
Z
Seth
P
P
D000256:Adenoviridae / Q000235:genetics*; D000998:Antiviral Agents / Q000633:toxicity*; D002051:Burkitt Lymphoma; D002470:Cell Survival / Q000187:drug effects*; D015774:Ganciclovir / Q000633:toxicity*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics*; D006689:Hodgkin Disease; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D008223:Lymphoma; D016403:Lymphoma, Large B-Cell, Diffuse; D009101:Multiple Myeloma; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics
D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir