Journal
NANO LETTERS
Volume 18, Issue 3, Pages 1916-1924Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.7b05284
Keywords
Immunotherapy; nanoparticle; CD8+T cell; artificial antigen presenting cell; magnetic clustering immune synapse
Categories
Funding
- National Science Foundation [DGE-1232825]
- NIH Cancer Nanotechnology Training Center at the JHU Institute for Nanobiotechnology [2T32CA153952-06]
- National Cancer Institute of the NIH [F31CA206344]
- NIH Cancer Nanotechnology Training Center at the Johns Hopkins Institute for NanoBioTechnology
- ARCS foundation
- National Institutes of Health [P01-AI072677, R01-CA108835, R21-CA185819]
- TEDCO/Maryland Innovation Initiative
- CTOT-22 [U01AI113315]
- CTOT Ancillary [U01AI063594-14]
- Wojcicki-Troper Foundation
- Coulter Foundation
- NATIONAL CANCER INSTITUTE [R21CA185819] Funding Source: NIH RePORTER
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T cell activation requires the coordination of a variety of signaling molecules including T cell receptor-specific signals and costimulatory signals. Altering the composition and distribution of costimulatory molecules during stimulation greatly affects T cell functionality for applications such as adoptive cell therapy (ACT), but the large diversity in these molecules complicates these studies. Here, we develop and validate a reductionist T cell activation platform that enables streamlined customization of stimulatory conditions. This platform is useful for the optimization of ACT protocols as well as the more general study of immune T cell activation. Rather than decorating particles with both signal 1 antigen and signal 2 costimulus, we use distinct, monospecific, paramagnetic nanoparticles, which are then clustered on the cell surface by a magnetic field. This allows for rapid synthesis and characterization of a small number of single-signal nanoparticles which can be systematically combined to explore and optimize T cell activation. By increasing cognate T cell enrichment and incorporating additional costimulatory molecules using this platform, we find significantly higher frequencies and numbers of cognate T cells stimulated from an endogenous population. The magnetic field-induced association of separate particles thus provides a tool for optimizing T cell activation for adoptive immunotherapy and other immunological studies.
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