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 W Kinzler, Shibin Zhou, Bert Vogelstein, Jonathan P Schneck

Research output: Contribution to journalArticle

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

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T-cells
antigens
Tumors
tumors
expansion
cells
Epitopes
streamlining
costs
Neoplasm Antigens
Antigens
mice
Antigen-Presenting Cells
Costs
regression analysis
cancer

Keywords

  • adoptive immunotherapy
  • immunotherapy
  • nanoparticles

ASJC Scopus subject areas

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

Cite this

Enrichment and Expansion with Nanoscale Artificial Antigen Presenting Cells for Adoptive Immunotherapy. / Perica, Karlo; Bieler, Joan Glick; Schütz, Christian; Varela, Juan Carlos; Douglass, Jacqueline; Skora, Andrew; Chiu, Yen Ling; Oelke, Mathias; Kinzler, Kenneth W; Zhou, Shibin; Vogelstein, Bert; Schneck, Jonathan P.

In: ACS Nano, Vol. 9, No. 7, 28.07.2015, p. 6861-6871.

Research output: Contribution to journalArticle

Perica K, Bieler JG, Schütz C, Varela JC, Douglass J, Skora A et al. Enrichment and Expansion with Nanoscale Artificial Antigen Presenting Cells for Adoptive Immunotherapy. ACS Nano. 2015 Jul 28;9(7):6861-6871. https://doi.org/10.1021/acsnano.5b02829
Perica, Karlo ; Bieler, Joan Glick ; Schütz, Christian ; Varela, Juan Carlos ; Douglass, Jacqueline ; Skora, Andrew ; Chiu, Yen Ling ; Oelke, Mathias ; Kinzler, Kenneth W ; Zhou, Shibin ; Vogelstein, Bert ; Schneck, Jonathan P. / Enrichment and Expansion with Nanoscale Artificial Antigen Presenting Cells for Adoptive Immunotherapy. In: ACS Nano. 2015 ; Vol. 9, No. 7. pp. 6861-6871.
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