CLONOGENIC NATURAL KILLER (NK) CELL POPULATIONS AND METHODS OF PRODUCING AND USING SUCH POPULATIONS

摘要

The present invention relates to novel methods for in vitro expansion of clonogenic natural killer (NK) cells. The methods utilize the stimulatory effects of trans-presented IL-15 in cell culture using feeder cells to expand isolated NK cell clones with a predetermined phenotypic trait of interest. The resultant clonogenic NK cell populations are homogenous, in contrast to heterogenous, crude NK cells typically isolated and expanded from a human tissue sample. The present invention also relates to feeder cells that are genetically engineered to trans-present IL-15 involving co-expressing human IL-15 and IL-15 receptor α subunit (IL-15Rα) that are capable of stimulating the expansion of NK cell clones in vitro. The present invention further relates to viable, functional clonogenic NK cell populations with the predetermined phenotypic trait of interest obtained via the above in vitro expansion methods and their use in personalized medicine to treat diseases, including leukemia, lymphoma and human hematopoietic cell transplantation (HCT), in drug screening and in basic and translational studies involving NK cells.