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Mol Ther. 2014 Feb;22(2):420-429. doi: 10.1038/mt.2013.249. Epub 2013 Oct 25.

Maraba virus as a potent oncolytic vaccine vector.

Author information

1
McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
2
McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Ontario Veterinary College, University of Guelph, Toronto, Ontario, Canada.
3
McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
4
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
5
McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: lichtyb@mcmaster.ca.

Abstract

The rhabdovirus Maraba has recently been characterized as a potent oncolytic virus. In the present study, we engineered an attenuated Maraba strain, defined as MG1, to express a melanoma-associated tumor antigen. Its ability to mount an antitumor immunity was evaluated in tumor-free and melanoma tumor-bearing mice. Alone, the MG1 vaccine appeared insufficient to prime detectable adaptive immunity against the tumor antigen. However, when used as a boosting vector in a heterologous prime-boost regimen, MG1 vaccine rapidly generated strong antigen-specific T-cell immune responses. Once applied for treating syngeneic murine melanoma tumors, our oncolytic prime-boost vaccination protocol involving Maraba MG1 dramatically extended median survival and allowed complete remission in more than 20% of the animals treated. This work describes Maraba virus MG1 as a potent vaccine vector for cancer immunotherapy displaying both oncolytic activity and a remarkable ability to boost adaptive antitumor immunity.

PMID:
24322333
PMCID:
PMC3916044
DOI:
10.1038/mt.2013.249
[Indexed for MEDLINE]
Free PMC Article

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