A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
05
11
2021
accepted:
31
05
2022
pubmed:
6
7
2022
medline:
17
12
2022
entrez:
5
7
2022
Statut:
ppublish
Résumé
Systematically identifying synergistic combinations of targeted agents and immunotherapies for cancer treatments remains difficult. In this study, we integrated high-throughput and high-content techniques-an implantable microdevice to administer multiple drugs into different sites in tumors at nanodoses and multiplexed imaging of tumor microenvironmental states-to investigate the tumor cell and immunological response signatures to different treatment regimens. Using a mouse model of breast cancer, we identified effective combinations from among numerous agents within days. In vivo studies in three immunocompetent mammary carcinoma models demonstrated that the predicted combinations synergistically increased therapeutic efficacy. We identified at least five promising treatment strategies, of which the panobinostat, venetoclax and anti-CD40 triple therapy was the most effective in inducing complete tumor remission across models. Successful drug combinations increased spatial association of cancer stem cells with dendritic cells during immunogenic cell death, suggesting this as an important mechanism of action in long-term breast cancer control.
Identifiants
pubmed: 35788566
doi: 10.1038/s41587-022-01379-y
pii: 10.1038/s41587-022-01379-y
pmc: PMC9750874
doi:
Substances chimiques
Panobinostat
9647FM7Y3Z
Antineoplastic Agents
0
Banques de données
figshare
['10.6084/m9.figshare.19719421', '10.6084/m9.figshare.19719499', '10.6084/m9.figshare.19719514']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1823-1833Subventions
Organisme : NCI NIH HHS
ID : U54 CA209988
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA223150
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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