Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3499-3508
Adenovirus-Mediated Cytotoxicity of Chronic Lymphocytic Leukemia Cells
Daniel J. Medina,
Wendy Sheay,
Lauri Goodell,
Pamela Kidd,
Eileen White,
Arnold B. Rabson, and
Roger K. Strair
From The Cancer Institute of New Jersey and the Department of
Pathology, Robert Wood Johnson Medical School, University of Medicine
and Dentistry of New Jersey, New Brunswick, NJ; the Howard Hughes
Medical Institute and the Department of Molecular Biology and
Biochemistry, Rutgers University, Piscataway, NJ; the Center for
Advanced Biotechnology and Medicine, University of Medicine and
Dentistry of New Jersey, Piscataway, NJ; and the Department of
Molecular Genetics and Microbiology, Robert Wood Johnson Medical
School, University of Medicine and Dentistry of New Jersey, Piscataway,
NJ.
We have studied adenovirus-mediated cytotoxicity after infection of
malignant cells obtained from patients with chronic lymphocytic leukemia (CLL). Our studies indicate that adenoviruses can infect primary CLL cells and that infection of CLL cells with a
replication-competent strain of human adenovirus 5 (Ad5dl309) results in cytotoxicity. Adenovirus-mediated
cytotoxicity was also seen after infection of CLL cells with a variety
of viruses attenuated by mutations in the adenovirus early region 1 (E1) or early region 2 (E2). Even viruses attenuated by deletion of the
entire E1 region resulted in cytotoxicity after infection of the CLL
cells obtained from some patients. Although there was variability in
the degree of cytotoxicity induced by different viruses in different
patients cells, a virus with a mutation in the E1B 19K gene resulted in the greatest degree of cytotoxicity in most of the CLL samples tested.
These studies demonstrate that infection of CLL cells by attenuated
adenoviruses with specific mutations in the E1 or E2 region results in
cell death. Attenuated adenoviruses should be developed further as
therapeutic agents for patients with CLL.
