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Enrichment and expansion with nanoscale artificial antigen presenting cells for T cell adoptive immunotherapy
  1. Karlo Perica1,
  2. Joan Bieler1,
  3. Christian Schuetz1,
  4. Juan Varela1,
  5. Mathias Oelke1 and
  6. Jonathan Schneck2
  1. Aff1 grid.21107.350000000121719311Johns Hopkins School of Medicine Baltimore Maryland United States
  2. Aff2 grid.21107.350000 0001 2171 9311Johns Hopkins School of Medicine, Department of PathologyInstitute for Cell Engineering Baltimore Maryland United States

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Meeting abstracts

Adoptive T cell therapy can mediate durable regression of cancer [1]. While pre-existing anti-tumor responses can only be cultured from a minority of cancer patients [2], T cells specific for a wide variety of tumor antigens can be generated by stimulation of naive precursor cells with tumor antigen [3]. This culture process relies on autologous antigen presenting cells and feeder cells, which are complex biologics that must be generated for each individual patient [4], 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 [5]. 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.


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