Adaptive Nanoparticle Platforms for High Throughput Expansion and Detection of Antigen-Specific T cells

John W. Hickey, Ariel Isser, Sebastian F. Salathe, Kayla M. Gee, Meng Hsuan Hsiao, Wasamah Shaikh, Nkechi C. Uzoukwu, Joan Glick Bieler, Hai Quan Mao, Jonathan P. Schneck

Research output: Contribution to journalArticlepeer-review

Abstract

T cells are critical players in disease; yet, their antigen-specificity has been difficult to identify, as current techniques are limited in terms of sensitivity, throughput, or ease of use. To address these challenges, we increased the throughput and translatability of magnetic nanoparticle-based artificial antigen presenting cells (aAPCs) to enrich and expand (E+E) murine or human antigen-specific T cells. We streamlined enrichment, expansion, and aAPC production processes by enriching CD8+ T cells directly from unpurified immune cells, increasing parallel processing capacity of aAPCs in a 96-well plate format, and designing an adaptive aAPC that enables multiplexed aAPC construction for E+E and detection. We applied these adaptive platforms to process and detect CD8+ T cells specific for rare cancer neoantigens, commensal bacterial cross-reactive epitopes, and human viral and melanoma antigens. These innovations dramatically increase the multiplexing ability and decrease the barrier to adopt for investigating antigen-specific T cell responses.

Original languageEnglish (US)
Pages (from-to)6289-6298
Number of pages10
JournalNano Letters
Volume20
Issue number9
DOIs
StatePublished - Sep 9 2020

Keywords

  • Adoptive T cell therapy
  • Antigen-specific T cells
  • Artificial antigen presenting cell
  • Detection
  • High-throughput
  • Magnetic nanoparticle
  • Multiplexed
  • Neoantigen
  • Rare cell enrichment

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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