Browsing by Author "Kim, Hansol"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Cultivation of Natural Killer Cell for Immunotherapy(2018-04) Kim, HansolNatural Killer (NK) cells are a type of blood immune cells that are capable of lyse the infected or transformed cells without prior sensitization. Due to a small fraction of NK cells within human bodies, and the fact that the cells are not able to expand to lyse the target cells, cells were isolated from human blood, and were expanded. NK cells expanded without feeder cells showed only a small number of fold expansion. However, when the NK cells were co-cultivated with artificial Antigen Presenting Cells (aAPCs), NK cells showed a much greater number of fold expansion. Especially, NK cells co-cultured with K562 cells with membrane bound IL-21 (K562.mbIL21) showed about 10,000-fold expansion for 14 days cultivation. Continuous cultivation of NK cells with the K562.mbIL21 showed more than 100 billion-fold expansion for 30 days before it shows senescence. By employing a multivariate analysis technique, phenotypic changes during the activation and expansion of NK cells were captured. In addition, various kinetic parameters during the cultivation were identified to provide preliminary data for future research. It was found that NK cells could expand with dead aAPCs and their debris, showing a possibility of expanding NK cells without feeder cells since the K562 cells are cancerous, thus, they need to be completely removed for clinical use in promoting NK cells in the field of adoptive immunotherapy.Item Harnessing Natural Killer Cells for Improved Therapeutic Potential(2021-08) Kim, HansolCellular immunotherapy provides durable control for infected and transformed cells. However, current Natural Killer (NK) cell therapy products are limited by effector persistence. To this end, three strategies to improve the efficacy of NK cell-based therapies are discussed. Killer immunoglobulin-like receptors (KIR) are developed during maturation of NK cells. It showed that KIR develops primarily between CD56brightCD94high and CD56dimCD94high stages. Major demethylation activities were observed during the development of KIR at its proximal promoter region. Ascorbic acid showed to facilitate the development of KIR in collaboration with Ten-eleven translocation (TET) enzymes. NK cells with adaptive immunological properties persist and expand in response to cytomegalovirus (CMV) infection. The levels of intracellular metabolites were analyzed and showed that adaptive NK cells have relatively higher levels of metabolites associated with glycolysis, purine, and pyrimidine metabolism. This supports the notion that adaptive NK cells have upregulated metabolic profiles, and have capacity to expand upon reactivation of CMV which is similar to the characteristics of memory T cells. To address challenges associated with inconsistencies of the manufactured product, and treatment cost, we developed a triple gene-edited induced pluripotent stem cell (iPSC) platform for broad patient-based adoptive cell therapy. First edit is to introduce non-cleavable CD16 which prevents reduced efficacy by antibody-dependent cellular cytotoxicity (ADCC). Second edit allows iPSC-derived NK cells, termed iNK, to persist without supplementation of exogenous IL-15 by introducing IL-15 receptor fusion. The last edit was to avoid daratumumab-induced fratricide by knocking out CD38 on the surface of the iNK cells. These engineered iNK cells persisted in vivo without supplementation of exogenous cytokine and could be combined with daratumumab for enhanced treatment of multiple myeloma. The gene-edited iNK cells exhibited metabolic features and gene expression profiles similar to those of adaptive NK cells which has broad off-the-shelf potential for the treatment of advanced cancer.