Cell-derived nanoparticles generated from cell-based artificial antigen presenting cells allow for the robust and rapid manufacturing of patient T cells 9064

Abstract Description Some individuals are unable to receive chimeric antigen receptor T cells (CAR-Ts) due to the inability to manufacture their T cells. We hypothesized that a cell-based scaffold that was able to deliver multiple costimulatory and cytokine signals could expand T cells more effectively than current platforms, resulting in the ability for more individuals to benefit from CAR-T therapy. To test this, we generated an array of K562-based aAPCs and found that aAPCs that used an OKT3-based scFv to deliver signal 1, CD86 and 4-1BBL to deliver costimulatory signals and produced IL-7 and IL-15 to provide cytokine support were able to robustly expand T cells. We manufactured cell-derived nanoparticles (CDNPs) from these aAPCs that were able to decrease the time needed for T cells to complete their first cell division compared to synthetic, agonist antibody coated beads and were able to generate highly functional CAR-T cells. Importantly, CDNPs were able to robustly expand T cells from 15 patient donors, including 5 samples that could not be manufactured using state of the art approaches. Lastly, CAR-Ts manufactured by CDNPs, especially those that used an accelerated manufacturing process, were able to eliminate tumors in vivo more effectively than CAR-Ts manufactured by anti-CD3/28 coated beads, providing the basis and rationale to use these CDNPs in the CAR-T manufacturing process. Funding Sources BlueWhale Bio Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)