Volume 2 Supplement 3
Enrichment and expansion with nanoscale artificial antigen presenting cells for T cell adoptive immunotherapy
© Perica et al.; licensee BioMed Central Ltd. 2014
Published: 6 November 2014
Adoptive T cell therapy can mediate durable regression of cancer . While pre-existing anti-tumor responses can only be cultured from a minority of cancer patients , T cells specific for a wide variety of tumor antigens can be generated by stimulation of naive precursor cells with tumor antigen . This culture process relies on autologous antigen presenting cells and feeder cells, which are complex biologics that must be generated for each individual patient , significantly increasing the cost and complexity of adoptive immunotherapy.
To quickly generate large numbers of functional tumor-specific T cells from naïve T cell precursors, we developed a T cell Enrichment+Expansion strategy using paramagnetic, nanoscale artificial Antigen Presenting Cells (nano-aAPC), which are capable of enriching rare tumor-specific T cells in a magnetic column and activating them. We generated up to 150,000 total Trp2-specific cells in only one week from 10 million polyclonal CD8 lymphocytes containing approximately 10 precursor cells . Similar results were obtained for other tumor and model antigens, including the human tumor antigens A2-NY-ESO1 and A2-MART1. We further demonstrate that removing irrelevant bystander cells by enrichment confers a significant survival and proliferation advantage to tumor-specific T cells both during in vitro culture and after adoptive transfer in vivo. Streamlining the generation of large numbers of high-frequency tumor-specific T cells in a cost effective, reproducible fashion through Enrichment+Expansion could be a powerful addition to autologous tumor immunotherapy protocols.
- Restifo NP, Dudley ME, Rosenberg Sa: Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012, 12: 269-81. 10.1038/nri3191.View ArticlePubMedGoogle Scholar
- Dudley ME, Rosenberg Sa: Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat Rev Cancer. 2003, 3: 666-75. 10.1038/nrc1167.PubMed CentralView ArticlePubMedGoogle Scholar
- Yee C: The use of endogenous T cells for adoptive transfer. Immunol. Rev. 2014, 257: 250-63. 10.1111/imr.12134.View ArticlePubMedGoogle Scholar
- Itzhaki O, Hovav E, Ziporen Y, Levy D, Kubi A, Zikich D, Hershkovitz L, Trevess AJ, Shalmon B, Zippel D, Markel G, Shapira-frommer R, Schachter J, MJBJ : Establishment and Large-scale Expansion of Minimally Adoptive Transfer Therapy. J Immunother. 2011, 34: 212-220.View ArticlePubMedGoogle Scholar
- Jenkins MK, Chu HH, McLachlan JB, JL : Moon, On the composition of the preimmune repertoire of T cells specific for Peptide-major histocompatibility complex ligands. Annu Rev Immunol. 2010, 28: 275-94. 10.1146/annurev-immunol-030409-101253.View ArticlePubMedGoogle Scholar
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