TY - JOUR
T1 - Magnetic field-induced t cell receptor clustering by nanoparticles enhances t cell activation and stimulates antitumor activity
AU - Perica, Karlo
AU - Tu, Ang
AU - Richter, Anne
AU - Bieler, Joan Glick
AU - Edidin, Michael
AU - Schneck, Jonathan P.
PY - 2014/3/25
Y1 - 2014/3/25
N2 - 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.
AB - 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.
KW - T cell
KW - adoptive immunotherapy
KW - cancer immunotherapy
KW - magnetic nanoparticles
KW - membrane organization
KW - receptor clustering
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U2 - 10.1021/nn405520d
DO - 10.1021/nn405520d
M3 - Article
C2 - 24564881
AN - SCOPUS:84896991574
VL - 8
SP - 2252
EP - 2260
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 3
ER -