Optimized expansion and transduction protocol for primary human CAR-NK cell manufacturing
Pfefferle A, Contet J, Wong K, et al. Optimisation of a Primary Human CAR-NK Cell Manufacturing Pipeline. Clinical and Translational Immunology. 2024; 13 (5) (doi: 10.1002/cti2.1507).
Scientists have improved on the process for using allogeneic natural killer (NK) cells in chimeric antigen receptor (CAR) immunotherapy. Incorporating allogeneic NK cells as the foundation of CAR treatment promises to avoid the higher costs and significant toxicities associated with using autologous T cells, but current manufacturing processes are less than optimal. Investigators identified a novel approach that markedly enhances lentiviral transduction efficiency of primary human NK cells, which they paired with a novel in vitro expansion protocol. The technique produces clinically relevant doses of CAR-NK cells with robust on-target serial killing. Additionally, NK cells derived from adult peripheral blood were found to be superior to those derived from umbilical cord blood (CB) as the source for generating a CAR-NK cell product. Cryopreservation sensitivity, restricted starting cell number, and reduced overall expansion of CB-NK cells remain barriers to leveraging CB-derived CAR-NK cells in this refined protocol.