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ACS Nano. 2015 Jul 28;9(7):6861-71. doi: 10.1021/acsnano.5b02829. Epub 2015 Jul 14.

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

Author information

1
∥Ludwig Cancer Research Center and Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, United States.

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.

KEYWORDS:

adoptive immunotherapy; immunotherapy; nanoparticles

PMID:
26171764
PMCID:
PMC5082131
DOI:
10.1021/acsnano.5b02829
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

COMPETING FINANCIAL INTERESTS: Under a licensing agreement between NexImmune and the Johns Hopkins University, JPS and MO are entitled to a share of royalty received by the University on sales of products derived from this article. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

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