Gene modification of human natural killer cells using a retroviral vector

Abstract

As part of the innate immune system, natural killer (NK) cells are regarded as promising effector cells for adoptive cell therapy approaches to treat patients with cancer. In some cases, genetic modification of the NK cells may be considered but such manipulation has to be integrated into the expansion method to allow the generation of clinically relevant numbers of gene-modified NK cells. Therefore, an efficient gene transfer procedure is needed. Our group developed a retrovirus-based transduction protocol capable of robust expansion of genemodified NK cells with a high rate of transgene expression. Actively dividing cells is a prerequisite for efficient gene transfer when using a retroviral vector. In the procedure presented here, strong activation of the NK cells was provided by a combination of IL-15 and the K-562 feeder cells. Beside the interest in developing a simple procedure compliant with good manufacturing practice (GMP) for the production of therapeutic products, this approach also provides a valuable means of generating genetically modified primary NK cells for future preclinical studies.