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Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia

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.

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Acknowledgements

We thank the members of the Molecular Oncology Group, Lady Davis Institute, and McGill University for helpful discussions. We also thank Lama Fawaz for helpful discussions. This research was supported by grants from the National Cancer Institute with funds from the Canadian Cancer Society to JH and JB, the Canadian Institutes of Health Research and CANVAC, and the Canadian Network for Vaccines and Immunotherapeutics (to JH). ESA is supported by a Fellowship from the FRSQ and JH is a recipient of a CIHR Senior Investigator award.

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Correspondence to J Hiscott.

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Césaire, R., Olière, S., Sharif-Askari, E. et al. Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia. Oncogene 25, 349–358 (2006). https://doi.org/10.1038/sj.onc.1209055

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