NUK - logo
E-viri
Celotno besedilo
Recenzirano
  • SIMPLIFYING IPSC TO NK MANU...
    Mata, M.F.; Guenat, J.; Henry, M.; Fernandez, V.D.; Tregidgo, M.; Jayawardena, M.; Statham, P.; Lee-Reeves, C.; Karachaliou, A.; Zingaro, S.; Nair, A.; Podovei, A.; O'Grady, C.; Marginean, D.; Tarunina, M.; Ponomaryov, T.; Hasan, J.

    Cytotherapy (Oxford, England), June 2024, Letnik: 26, Številka: 6
    Journal Article

    NK cells present an attractive alternative for immune cell therapy given their ability to kill multiple cells through non-MHC-restrictive effects and more favourable adverse event profiles compared to CAR-T cell therapies. Generation of clinical material is currently limited to patient or healthy donor-derived NK cells which are manipulated ex vivo to expand and genetically modify before administration and requires careful control of starting material through donor selection and screening. Truly allogeneic NK cell therapy can be attained through the differentiation of pluripotent stem cells to NK-like cells, thereby alleviating the need for selecting and maintaining donors and standardising starting material, as well as providing a near-unlimited source of cells through culture expansion. Here we describe a process for generating pluripotent stem cell starting material in a scalable automated bioreactor system which is then used to produce NK-like cells demonstrating high purity and capable of killing multiple cancer cell types. Pluripotent stem cell expansion yielded >8E6 viable cells/mL expressing and NK productivity was 24-fold higher compared to the equivalent well plate process. Extensive process characterisation revealed critical process parameters linked to increased NK yield and function beyond the scope of traditionally utilised analytical methods. The developed process has the potential to meet expected clinical demand once scaled and further improves the manufacturability of pluripotent stem cell-derived cell therapies through automation and cost-reduction.