Cell-derived Nanoparticles Provide a Robust Platform to Manufacture Therapeutic T cells.

Some patients cannot receive T cell therapies because their cells are unable to be manufactured. To address this limitation, we developed K562-based artificial antigen-presenting cells (aAPCs) expressing an OKT3-derived scFv for TCR stimulation, CD86 and 4-1BBL for costimulation, and membrane-bound IL-7 and IL-15Rα/IL-15 for cytokine support. From these aAPCs, we generated cell-derived nanoparticles (CDNPs) that accelerated T cell entry into the cell cycle compared with CD3/28-coated beads, enabling efficient concurrent activation and lentiviral transduction. CDNPs robustly expanded T cells from patients whose products could not be manufactured using standard approaches, and these CDNP-derived CAR T cells controlled tumors in humanized mouse models. In a phase I trial of patients with CD19+ malignancies (NCT04684563), cGMP-compatible CDNPs enabled streamlined 3-day manufacturing of IL-18-expressing CD19 CAR T cells, yielding higher cell recovery and durable clinical responses without unexpected toxicities, supporting CDNPs as a platform for commercial CAR T cell production.