Modulating viscosity improves lentiviral transduction of NK cells: A simple solution to a persistent problem.

Genetically modified cell therapies (GMCT) hold potential for the treatment of cancer, autoimmune conditions, and rare diseases. A major determinant of GMCT success is modification efficiency, yet transducing certain cells of interest, such as primary natural killer (NK) cells, remains challenging. Major barriers to widespread adoption of GMCT are cost and difficulty of scale. Therefore, improving transduction rates with accessible, good manufacturing practices (GMP) compatible reagents may help reduce this barrier and prevent manufacturing failure. We show that using a modified viscous transduction medium (VTM) made with methyl-cellulose significantly increased the transduction efficiency of primary human NK cells without affecting viability, expansion, or function. VTM outperformed commercially available transduction enhancers. Transduction with VTM significantly improved the yield of anti-CD22 chimeric antigen receptor (CAR)-NK cells. Moreover, VTM was similarly effective at improving the transduction of primary T cells and hematopoietic stem cells. Overall, VTM may provide a simple, cost-effective, and GMP-compliant solution to increase the yield of genetically modified immune cells for immunotherapy. This may improve the efficacy of immunotherapies and reduce the overall costs of production.