Abstract 2755: Transcriptomic changes experienced by activated and expanded NK cells for their use in the treatment of hematological malignancies

Abstract

Abstract Natural Killer (NK) cells have shown great promise as a viable cell-based cancer immunotherapy. We have developed a protocol that produces expanded and highly activated NK (eNK) cells from healthy human donors that have been shown to be effective alone and in combination with monoclonal antibodies in a variety of hematological malignancies. The eNK cells showed a dramatic increase in cytolytic capacity after their expansion and activation using IL-2, IL-15, and 721.221 feeder cells. In order to elucidate the underlying mechanisms behind the changes, mRNAseq and miRNA arrays were performed on mRNA and miRNA samples, respectively, extracted from several NK expansions, taken at Day 0 (before activation) and Day 20 (after activation and expansion). Bioinformatic analysis was performed to identify differential gene expression changes and their downstream effects. Based on the genes with greatest differential expression, we quantified their corresponding proteins using flow cytometry, western blots, and ELISAs. Results reveal several discrete changes in the transcriptome that are reflected in changes in protein expression levels within the eNK cells. We conclude that the increased cytolytic capacity of eNK cells is due to the synergistic effect of variations in different genes responsible for target recognition, effector function, cell cycle progression and cell survival. These data can be used in the future to produce better eNK cells as treatment for hematological malignancies. Citation Format: Chantal Reina-Ortiz, Pilar Mozas Alonso, Alberto Cebollada, David Ovelleiro, Luis Alberto Anel Bernal. Transcriptomic changes experienced by activated and expanded NK cells for their use in the treatment of hematological malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2755.