Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma
Open Access
- 22 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 34 (12), 3310-3322
- https://doi.org/10.1038/s41375-020-0828-7
Abstract
Oncolytic virus therapy leads to immunogenic death of virus-infected tumor cells and this has been shown in preclinical models to enhance the cytotoxic T-lymphocyte response against tumor-associated antigens (TAAs), leading to killing of uninfected tumor cells. To investigate whether oncolytic virotherapy can increase immune responses to tumor antigens in human subjects, we studied T-cell responses against a panel of known myeloma TAAs using PBMC samples obtained from ten myeloma patients before and after systemic administration of an oncolytic measles virus encoding sodium iodide symporter (MV-NIS). Despite their prior exposures to multiple immunosuppressive antimyeloma treatment regimens, T-cell responses to some of the TAAs were detectable even before measles virotherapy. Measurable baseline T-cell responses against MAGE-C1 and hTERT were present. Furthermore, MV-NIS treatment significantly (P < 0.05) increased T-cell responses against MAGE-C1 and MAGE-A3. Interestingly, one patient who achieved complete remission after MV-NIS therapy had strong baseline T-cell responses both to measles virus proteins and to eight of the ten tested TAAs. Our data demonstrate that oncolytic virotherapy can function as an antigen agnostic vaccine, increasing cytotoxic T-lymphocyte responses against TAAs in patients with multiple myeloma, providing a basis for continued exploration of this modality in combination with immune checkpoint blockade.Funding Information
- Division of Cancer Prevention, National Cancer Institute (R01CA125614)
- Al and Mary Agnes McQuinn, the Harold W. Siebens Charitable Foundation, and the Richard M. Schulze Family Foundation.
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