Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
14
11
2019
accepted:
30
03
2020
revised:
13
03
2020
pubmed:
25
4
2020
medline:
5
1
2021
entrez:
25
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32327728
doi: 10.1038/s41375-020-0828-7
pii: 10.1038/s41375-020-0828-7
pmc: PMC7581629
mid: NIHMS1607335
doi:
Substances chimiques
Antigens, Neoplasm
0
Symporters
0
sodium-iodide symporter
4XE5NDT4K1
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3310-3322Subventions
Organisme : NCI NIH HHS
ID : P50 CA186781
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA125614
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA168719
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000135
Pays : United States
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