Adenovirus-mediated cytotoxicity of chronic lymphocytic leukemia cells.
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.
Medina
D J
DJ
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 08901, USA.
Sheay
W
W
Goodell
L
L
Kidd
P
P
White
E
E
Rabson
A B
AB
Strair
R K
RK
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017500:Adenovirus E1A Proteins / Q000235:genetics; D017501:Adenovirus E1B Proteins / Q000235:genetics; D017502:Adenovirus E2 Proteins / Q000235:genetics; D000970:Antineoplastic Agents; D017209:Apoptosis; D001402:B-Lymphocytes / Q000821:virology; D017353:Gene Deletion; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000821:virology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D017502:Adenovirus E2 Proteins; D000970:Antineoplastic Agents