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

## TL;DR

Researchers developed a new method using cell-derived nanoparticles to efficiently manufacture therapeutic T cells, even for patients who previously couldn't receive such treatments.

## Contribution

A novel platform using cell-derived nanoparticles was developed to improve T cell manufacturing and CAR T cell therapy.

## Key findings

- CDNPs accelerated T cell activation and transduction compared to traditional methods.
- CDNP-derived CAR T cells controlled tumors in humanized mouse models.
- A phase I trial showed CDNPs enabled efficient and safe CAR T cell production with durable clinical responses.

## Abstract

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.