From byproduct to biotherapeutic: Comparative study of buffy coats and leukoreduction system chambers for NK cell-based immunotherapies

Natural killer (NK) cell immunotherapies require reliable access to large numbers of functionally consistent cells, yet obtaining sufficient material remains challenging. Therefore, we evaluated leukoreduction system chambers (LRSCs), routinely discarded after plateletpheresis, as a low-cost and logistically accessible addition to buffy coats (BCs) for NK cell isolation. Although LRSCs contain less volume than BCs, they provide higher concentrations of mononuclear cells and NK cells. The total NK yield per unit is lower, but viability and cytotoxic function are comparable to BCs. LRSC-derived NK cells display increased NKp46 and NKG2A expression with a higher proportion of CD56^bright cells. They also show enhanced proliferative capacity over sixteen days. Phenotyping of source materials reveals higher fractions of NK and B cells in LRSCs, suggesting effects of the donation modality or donor characteristics warranting further study. Altogether, our findings support LRSCs as a practical and economical NK cell source for research and method development with clear potential for clinical translation.