Magnetic field-induced t cell receptor clustering by nanoparticles enhances t cell activation and stimulates antitumor activity

Karlo Perica, Ang Tu, Anne Richter, Joan Glick Bieler, Michael Edidin, Jonathan P. Schneck

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2252-2260
Number of pages9
JournalACS Nano
Volume8
Issue number3
DOIs
StatePublished - Mar 25 2014

Keywords

  • T cell
  • adoptive immunotherapy
  • cancer immunotherapy
  • magnetic nanoparticles
  • membrane organization
  • receptor clustering

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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