Enrichment and Expansion with Nanoscale Artificial Antigen Presenting Cells for Adoptive Immunotherapy
Year: 2015
Type: article
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.
Source: ACS Nano
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Cancer Research Institute, Commonwealth Fund, Foundation for Women's Cancer, Virginia and D.K. Ludwig Fund for Cancer Research, Sol Goldman Charitable Trust, Deutsche Forschungsgemeinschaft, Miltenyi Biotec, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Troper Wojcicki Foundation
Awards: Medical Scientist Training Program, Antigen receptor inputs: linking structural, molecular, and cellular responses, G3900205185, Molecular Genetic Analysis of Colorectal Cancer, IMMUNOREGULATORY FUNCTIONS OF TCR AND MHC COMPLEXES, Training in Anti-Cancer Drug Development, Use of aAPC for Melanoma Adoptive Immunotherapy, SPORE in Gastrointestinal Cancers, Antigen Specific MOdulation of T Cell Responses, G8631071595, Training Program in Hematology, G979981402
OpenAlex ID: W2431286612
