Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia.
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.
Césaire
R
R
Laboratoire de Virologie-Immunologie and UMR433 INSERM, Centre Hospitalier Universitaire de Fort-de-France, Martinique, France.
Olière
S
S
Sharif-Askari
E
E
Loignon
M
M
Lézin
A
A
Olindo
S
S
Panelatti
G
G
Kazanji
M
M
Aloyz
R
R
Panasci
L
L
Bell
J C
JC
Hiscott
J
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D016923:Cell Death; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D006801:Humans; D015458:Leukemia, T-Cell / Q000628:therapy* / Q000821:virology*; D008213:Lymphocyte Activation; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*; D014779:Virus Replication