Journal
ACS NANO
Volume 9, Issue 7, Pages 6861-6871Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b02829
Keywords
immunotherapy; nanoparticles; adoptive immunotherapy
Categories
Funding
- National Institutes of Health [AI072677, GM 07309, AI44129, CA 43460, CA 62924, CA 09243, CA108835]
- Troper Wojcicki Foundation
- Virginia and D.K. Ludwig Fund for Cancer Research
- Sol Goldman Center for Pancreatic Cancer Research
- Commonwealth Foundation
- Miltenyi Biotec
- Nexlmmune
- Cancer Research Institute
- German Research Foundation (DFG) [SCHU-2681/1-1]
- HERA Women's Cancer Foundation [OSB1]
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Adoptive immunotherapy (All) 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 naive 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.
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