Journal
ACS NANO
Volume 8, Issue 3, Pages 2252-2260Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn405520d
Keywords
magnetic nanoparticles; cancer immunotherapy; T cell; adoptive immunotherapy; receptor clustering; membrane organization
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Funding
- National Institutes of Health [P01-AI072677, R01-AI44129, R01-CA108835]
- Miltenyi Biotec
- NexImmune
- Cancer Research Institute Predoctoral Fellowship
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Iron-dextran nanoparticles functionalized with T cell activating proteins have been used to study T cell receptor (TCR) signaling. However, nanoparticle triggering of membrane receptors is poorly understood and may be sensitive to physiologically regulated changes in TCR clustering that occur after T cell activation. Nano-aAPC bound 2-fold more TCR on activated T cells, which have clustered TCR, than on naive T cells, resulting in a lower threshold for activation. To enhance T cell activation, a magnetic field was used to drive aggregation of paramagnetic nano-aAPC, resulting in a doubling of TCR cluster size and increased T cell expansion in vitro and after adoptive transfer in vivo. T cells activated by nano-aAPC in a magnetic field inhibited growth of B16 melanoma, showing that this novel approach, using magnetic field-enhanced nano-aAPC stimulation, can generate large numbers of activated antigen-specific T cells and has clinically relevant applications for adoptive immunotherapy.
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