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- Title
Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia.
- Authors
Césaire, R.; Olière, S.; Sharif-Askari, E.; Loignon, M.; Lézin, A.; Olindo, S.; Panelatti, G.; Kazanji, M.; Aloyz, R.; Panasci, L.; Bell, J. C.; Hiscott, J.
- Abstract
Treatments for hematological malignancies have improved considerably over the past decade, but the growing therapeutic arsenal has not benefited adult T-cell leukemia (ATL) patients. Oncolytic viruses such as vesicular stomatitis virus (VSV) have recently emerged as a potential treatment of solid tumors and leukemias in vitro and in vivo. In the current study, we investigated the ability of VSV to lyse primary human T-lymphotropic virus type 1 (HTLV-1)-infected T-lymphocytes from patients with ATL. Ex vivo primary ATL cells were permissive for VSV and underwent rapid oncolysis in a time-dependent manner. Importantly, VSV infection showed neither viral replication nor oncolysis in HTLV-1-infected, nonleukemic cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and in naive CD4+ T-lymphocytes from normal individuals or in ex vivo cell samples from patients with chronic lymphocytic leukemia (CLL). Interestingly, activation of primary CD4+ T-lymphocytes with anti-CD3/CD28 monoclonal antibody, and specifically with anti-CD3, was sufficient to induce limited viral replication and oncolysis. However, at a similar level of T-cell activation, VSV replication was increased fourfold in ATL cells compared to activated CD4+ T-lymphocytes, emphasizing the concept that VSV targets genetic defects unique to tumor cells to facilitate its replication. In conclusion, our findings provide the first essential information for the development of a VSV-based treatment for ATL.Oncogene (2006) 25, 349–358. doi:10.1038/sj.onc.1209055; published online 26 September 2005
- Subjects
ADULT T-cell leukemia; CANCER patients; VESICULAR stomatitis; HTLV-I; PRELEUKEMIA; T cells
- Publication
Oncogene, 2006, Vol 25, Issue 3, p349
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1209055