1. Magnetic Field-Induced T Cell Receptor Clustering by Nanoparticles Enhances T Cell Activation and Stimulates Antitumor Activity
- Author
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Michael Edidin, Karlo Perica, Anne Richter, Jonathan P. Schneck, Ang A. Tu, and Joan G. Bieler
- Subjects
magnetic nanoparticles ,CD3 Complex ,T cell ,Iron ,T-Lymphocytes ,Melanoma, Experimental ,Receptors, Antigen, T-Cell ,General Physics and Astronomy ,Antigen-Presenting Cells ,02 engineering and technology ,Biology ,Lymphocyte Activation ,Immunotherapy, Adoptive ,Article ,03 medical and health sciences ,Interleukin 21 ,Mice ,medicine ,Cytotoxic T cell ,Animals ,General Materials Science ,IL-2 receptor ,Antigen-presenting cell ,Protein Structure, Quaternary ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,cancer immunotherapy ,ZAP70 ,T-cell receptor ,General Engineering ,CD28 ,Dextrans ,membrane organization ,021001 nanoscience & nanotechnology ,Cell biology ,medicine.anatomical_structure ,Magnetic Fields ,Immunology ,Nanoparticles ,Protein Multimerization ,0210 nano-technology ,adoptive immunotherapy ,receptor clustering - Abstract
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.
- Published
- 2014