Enrichment and Expansion with Nanoscale Artificial Antigen Presenting Cells for Adoptive Immunotherapy

Karlo Perica, Joan Glick Bieler, Christian Schütz, Juan Carlos Varela, Jacqueline Douglass, Andrew Skora, Yen Ling Chiu, Mathias Oelke, Kenneth Kinzler, Shibin Zhou, Bert Vogelstein, Jonathan P. Schneck

Research output: Contribution to journalArticlepeer-review

Abstract

Adoptive immunotherapy (AIT) can mediate durable regression of cancer, but widespread adoption of AIT is limited by the cost and complexity of generating tumor-specific T cells. Here we develop an Enrichment + Expansion strategy using paramagnetic, nanoscale artificial antigen presenting cells (aAPC) to rapidly expand tumor-specific T cells from rare naïve precursors and predicted neo-epitope responses. Nano-aAPC are capable of enriching rare tumor-specific T cells in a magnetic column and subsequently activating them to induce proliferation. Enrichment + Expansion resulted in greater than 1000-fold expansion of both mouse and human tumor-specific T cells in 1 week, with nano-aAPC based enrichment conferring a proliferation advantage during both in vitro culture and after adoptive transfer in vivo. Robust T cell responses were seen not only for shared tumor antigens, but also for computationally predicted neo-epitopes. Streamlining the rapid generation of large numbers of tumor-specific T cells in a cost-effective fashion through Enrichment + Expansion can be a powerful tool for immunotherapy.

Original languageEnglish (US)
Pages (from-to)6861-6871
Number of pages11
JournalACS Nano
Volume9
Issue number7
DOIs
StatePublished - Jul 28 2015

Keywords

  • adoptive immunotherapy
  • immunotherapy
  • nanoparticles

ASJC Scopus subject areas

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

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