Enrichment and Expansion with Nano-Artificial Antigen Presenting Cells for Adoptive Immunotherapy

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 one 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 not only seen 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. Nanoscale artificial antigen presenting cells (nano-aAPC) are synthesized by conjugating Major Histocompatibility Complex-Peptide and co-stimulatory anti-CD28 to a paramagnetic iron-dextran nanoparticle. Nano-aAPC are thus capable of binding tumor-specific T cells, capturing them in a magnetic column, and subsequently activating them, a process termed Enrichment+Expansion (E+E). E+E induced 1000-fold expansion of naïve tumor-specific cells in one week.