Table 1.

Factors affecting the ouctome of the manufacturing process of NK cell-based medicinal products.

Cell source

Bone marrow

Umbilical cord blood

Embryonic stem cells

Induced pluripotent stem cells

NK cell lines

Culture conditions

Cytokines (IL-2, IL-15, IL-12, IL-18)

Feeder cells (autologous PBMC, EBV-TCT-LCL, K562-mb15-41BBL)

Antibodies (anti-CD3, anti-CD52)

Genetic manipulation (retro- or lentiviral-based transduction, mRNA transfection)

Culture containers

Standard culture flasks

Culture bags

Gas-permeable static cell culture flasks

Bioreactors

Final product evaluation

Viability (live/dead)

Identity and contamination (CD56, CD16, CD3, CD14, CD45, CD19)

Yield

Phenotype (KIR, NKp44, NKp46, NKG2A, NKG2C)

Functionality (degranulation, cytokine release, target cell lysis, activation)