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

Area of Science:

• Immunology
• Biotechnology
• Oncology

Background:

• T cell therapies face manufacturing limitations for certain patient groups.
• Current methods may not be suitable for all patients requiring T cell-based treatments.

Purpose of the Study:

• To develop an alternative manufacturing platform for T cell therapies.
• To overcome limitations in T cell expansion and transduction for difficult-to-manufacture patient products.

Main Methods:

• Development of K562-based artificial antigen-presenting cells (aAPCs) engineered for T cell stimulation and support.
• Generation of cell-derived nanoparticles (CDNPs) from aAPCs for T cell activation and transduction.
• Evaluation of CDNPs in preclinical models and a Phase I clinical trial (NCT04684563) for CD19+ malignancies.

Main Results:

• CDNPs accelerated T cell cycle entry compared to traditional beads, enabling efficient concurrent activation and lentiviral transduction.
• CDNPs successfully expanded T cells from patients with previously unmanufacturable products.
• CDNP-derived CAR T cells demonstrated tumor control in humanized mouse models.
• A Phase I trial showed streamlined 3-day manufacturing of CD19 CAR T cells using cGMP-compatible CDNPs, with higher cell recovery and durable clinical responses.

Conclusions:

• CDNPs represent a promising platform for overcoming T cell manufacturing challenges.
• This approach enables efficient CAR T cell production for patients with difficult-to-manufacture cells.
• CDNPs support streamlined, commercial-scale CAR T cell production with positive clinical outcomes.