Serum-free Expansion of NK Cells with K562- Based Feeder Systems for Clinical Applications

My translational research program focuses on approaches to enhance the natural killer (NK) cell response to cancer, with an emphasis on ex vivo expansion and engineering of NK cells to improve number and function for adoptive immunotherapy. Our K562-based feeder cell method results in consistent, robust expansion of highly-active clinical-grade NK cells that enables repeated delivery of large cell doses for improved efficacy. This finding led to several first-in-human clinical trials evaluating adoptive immunotherapy with expanded NK cells under FDA Investigational New Drug applications. We are now building on this platform to develop universal-donor NK cell approaches that further improve the efficiency and cost, particularly when applied to genetic and non-genetic methods for improved tumor targeting and tissue homing. Researchers face a variety of regulatory challenges when developing the manufacturing platform for NK cells at clinical grade and scale. We have previously grown clinical-grade NK cells with irradiated feeder cells and media containing human or bovine serum; however, these critical reagents carry inherent regulatory and medical risks. In this talk I will describe our results in testing and implementing a novel, GMP-manufactured NK cell-optimized medium that in combination with a xeno-free, GMP-manufactured serum replacement supports NK cell cultures to clinically relevant scale, which is superior to that of standard media with serum supplements and does not compromise NK cell activity or phenotype.

 

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