In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 6, No. 27 ( 2020-07-03)
Abstract:
Many cancer patients not responding to current immunotherapies fail to produce tumor-specific T cells for various reasons, such as a lack of recognition of cancer cells as foreign. Here, we suggest a previously unidentified method for xenogenizing (turning self to non-self) tumors by using fusogenic exosomes to introduce fusogenic viral antigens (VSV-G) onto the tumor cell surface. We found that xenogenized tumor cells were readily recognized and engulfed by dendritic cells; thereby, tumor antigens were efficiently presented to T lymphocytes. Moreover, exosome–VSV-G itself acts as a TLR4 agonist and stimulates the maturation of dendritic cells, leading to CD8 + T cell cross-priming. The administration of these exosomes in multiple tumor mouse models xenogenized tumor cells, resulting in tumor growth inhibition. The combinatorial treatment with anti–PD-L1 exhibited complete tumor regression (30%) and better long-term overall survival. These results suggest that tumor xenogenization by fusogenic exosomes provides a previously unidentified novel strategy for cancer immunotherapy.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.aaz2083
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2020
detail.hit.zdb_id:
2810933-8
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