Efficient magnetic enrichment of antigen-specific T cells by engineering particle properties

John W. Hickey, Ariel Y. Isser, Fernando P. Vicente, Samuel B. Warner, Hai Quan Mao, Jonathan P Schneck

Research output: Contribution to journalArticle

Abstract

Magnetic particles can enrich desired cell populations to aid in understanding cell-type functions and mechanisms, diagnosis, and therapy. As cells are heterogeneous in ligand type, location, expression, and density, careful consideration of magnetic particle design for positive isolation is necessary. Antigen-specific immune cells have low frequencies, which has made studying, identifying, and utilizing these cells for therapy a challenge. Here we demonstrate the importance of magnetic particle design based on the biology of T cells. We create magnetic particles which recognize rare antigen-specific T cells and quantitatively investigate important particle properties including size, concentration, ligand density, and ligand choice in enriching these rare cells. We observe competing optima among particle parameters, with 300 nm particles functionalized with a high density of antigen-specific ligand achieving the highest enrichment and recovery of target cells. In enriching and then activating an endogenous response, 300 nm aAPCs generate nearly 65% antigen-specific T cells with at least 450-fold expansion from endogenous precursors and a 5-fold increase in numbers of antigen-specific cells after only seven days. This systematic study of particle properties in magnetic enrichment provides a case study for the engineering design principles of particles for the isolation of rare cells through biological ligands.

Original languageEnglish (US)
Pages (from-to)105-116
Number of pages12
JournalBiomaterials
Volume187
DOIs
StatePublished - Dec 1 2018

Keywords

  • Artificial antigen-presenting cells
  • Immunotherapy
  • Magnetic enrichment
  • Nanoparticles
  • Size
  • T cells

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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