Scalable production process development for NK cells targeting large-scale expansion.

Area of Science:

• Immunology
• Biotechnology
• Cell Therapy

Background:

• Natural Killer (NK) cells are promising for cancer immunotherapy due to lower Graft-Versus-Host Disease (GVHD) risk.
• Current NK cell expansion methods use scale-out strategies, hindering 'off-the-shelf' applications.
• Scalable bioreactor culture for induced pluripotent stem cell (iPSC)-derived NK cells remains underexplored.

Purpose of the Study:

• To develop and evaluate a scalable stirred bioreactor process for iPSC-derived NK cell expansion.
• To assess the impact of repeated stimulation and expansion on NK cell yield and quality.
• To demonstrate the feasibility of scaling up NK cell production from laboratory to pilot scale.

Main Methods:

• Developed a stirred culture system for iPSC-derived NK cell expansion.
• Employed repeated cycles of NK cell stimulation with agonist antibodies and expansion.
• Evaluated scale-up parameters using an aerated stirred bioreactor, transitioning from 1 L to 10 L.

Main Results:

• Stirred cultures significantly enhanced NK cell expansion compared to static cultures.
• Achieved a 1000-fold expansion of iPSC-derived NK cells with maintained quality through repeated cycles.
• Successfully scaled up production to 10 L bioreactors, yielding comparable cell expansion and quality.

Conclusions:

• Demonstrated a scalable aerated stirred bioreactor process for iPSC-derived NK cell expansion.
• The optimized process supports robust cell expansion and quality suitable for therapeutic applications.
• This scalable approach facilitates the clinical translation of 'off-the-shelf' NK cell therapies.