Broad application of adoptive cell transfer of tumor-specific T cells for the treatment of cancer has been limited. This is mainly due to the high cost and labor-intensive methods required to successfully generate autologous antigen-specific CD8+ T cells. Here, we report on a modified application of a novel nanoparticle-based method for expansion of tumor-specific CD8+ T cells from normal human donors. This Enrichment + Expansion (E+E) strategy uses paramagnetic, nanoscale artificial Antigen Presenting Cells (aAPC) to rapidly generate large numbers of tumor-specific CD8+ T cells from naïve precursors. Nano-aAPC are capable of enriching tumor-specific CD8+ T cells in a magnetic column and subsequently activating them to induce expansion.