Magnetic Field-Induced T Cell Receptor Clustering by Nanoparticles Enhances T Cell Activation and Stimulates Antitumor Activity

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.

Mechanisms of Cellular Effects Directly Induced by Magnetic Nanoparticles under Magnetic Fields

“…Cho et al applied a static magnetic field (0.2 T) to aggregate MNPs bound death receptor 4, which then promotes apoptosis signaling pathways [50]. Perica et al modified MNPs by T cell activating proteins to be artificial antigen presenting cells; when applying a magnetic field (0.15 T) the aggregation of MNPs resulted in the activation and expansion of T cells [51]. As shown in Table 2, we have also summarized other studies where mechanical force was used to regulate cells.…”

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

“…[89] In this direction, as an artificial APC, sub 100 nm sized iron oxide nanoparticles coated with dextran and conjugated with stimulatory molecules have shown to induce the T-cell receptor clustering under magnetic field and activate näive T cells. [90] More details on various nanoparticles strategies developed for cancer immunotherapy have been extensively reviewed elsewhere. [15,85,91] …”

Emerging nanotechnologies for cancer immunotherapy

“…Ex vivo stimulation of T cells with these particles in the presence of a magnetic fieldenhanced TCR clustering reduced the threshold of activation of T cells and improved the efficacy of adaptive T cell therapy. 81 Moreover, nanotechnology opens the door for the in vivo targeting, priming and expansion of T cells. For example, in vivo loading of T cells with lipid nanoparticle ''backpacks'' carrying stimulatory cytokines was demonstrated.…”