Engineered implantable vaccine platform for continuous antigen-specific immunomodulation.
Cancer vaccine
Immunomodulation
In situ delivery
Local controlled release
Oncoimmunotherapy
Subcutaneous implant
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
01
10
2021
revised:
03
01
2022
accepted:
12
01
2022
pubmed:
24
1
2022
medline:
14
4
2022
entrez:
23
1
2022
Statut:
ppublish
Résumé
Cancer vaccines harness the host immune system to generate antigen-specific antitumor immunity for long-term tumor elimination with durable immunomodulation. Commonly investigated strategies reintroduce ex vivo autologous dendritic cells (DCs) but have limited clinical adoption due to difficulty in manufacturing, delivery and low clinical efficacy. To combat this, we designed the "NanoLymph", an implantable subcutaneous device for antigen-specific antitumor immunomodulation. The NanoLymph consists of a dual-reservoir platform for sustained release of immune stimulants via a nanoporous membrane and hydrogel-encapsulated antigens for local immune cell recruitment and activation, respectively. Here, we present the development and characterization of the NanoLymph as well as efficacy validation for immunomodulation in an immunocompetent murine model. Specifically, we established the NanoLymph biocompatibility and mechanical stability. Further, we demonstrated minimally invasive transcutaneous refilling of the drug reservoir in vivo for prolonging drug release duration. Importantly, our study demonstrated that local elution of two drugs (GMCSF and Resiquimod) generates an immune stimulatory microenvironment capable of local DC recruitment and activation and generation of antigen-specific T lymphocytes within 14 days. In summary, the NanoLymph approach can achieve in situ immunomodulation, presenting a viable strategy for therapeutic cancer vaccines.
Identifiants
pubmed: 35066287
pii: S0142-9612(22)00013-8
doi: 10.1016/j.biomaterials.2022.121374
pmc: PMC8865051
mid: NIHMS1773907
pii:
doi:
Substances chimiques
Cancer Vaccines
0
Hydrogels
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
121374Subventions
Organisme : NCI NIH HHS
ID : U54 CA210181
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
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