Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3P Mediated Regulation
type: CreativeWork
description: Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion of human NK cells using K562 expressing membrane bound IL-21 (K562.mbIL21), and showed that K562.mbIL21 enables significantly higher expansion of functionally potent NK cells compared to K562.mbIL15. Both membrane bound IL15 (mbIL15) and membrane bound IL21 (mbIL21) expanded NK cells are currently in several Phase I/II clinical trials. K562.mbIL21 surpasses any other expansion to date not only in its rate of NK cell expansion, but also cytokine secretion, cytotoxicity, telomere length and MTOC synapse formation, yielding highly activated non-senescent cells. IL-15 and IL-21 signaling are essential for proliferation and activation of NK cells in vivo, yet mbIL21 far exceeds that of mbIL15 based expansion ex vivo. It is possible that mbIL21 expansion is better due to regulation of telomere length by promotion of telomerase activity by Stat 3, however this may not be the only determining factor. MiRNAs, crucial regulators of post-transcriptional gene regulation could play a role in causing the observed differences in proliferation in these 2 expansion systems. The role of miRNA in NK cells biology is an emerging area of interest and their effect on regulation of protein expression and function during expansion of NK cells remain to be studied. We hypothesize that activating and expanding human NK cells on membrane bound IL15 and membrane bound IL21 wi…
abstract: Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion of human NK cells using K562 expressing membrane bound IL-21 (K562.mbIL21), and showed that K562.mbIL21 enables significantly higher expansion of functionally potent NK cells compared to K562.mbIL15. Both membrane bound IL15 (mbIL15) and membrane bound IL21 (mbIL21) expanded NK cells are currently in several Phase I/II clinical trials. K562.mbIL21 surpasses any other expansion to date not only in its rate of NK cell expansion, but also cytokine secretion, cytotoxicity, telomere length and MTOC synapse formation, yielding highly activated non-senescent cells. IL-15 and IL-21 signaling are essential for proliferation and activation of NK cells in vivo, yet mbIL21 far exceeds that of mbIL15 based expansion ex vivo. It is possible that mbIL21 expansion is better due to regulation of telomere length by promotion of telomerase activity by Stat 3, however this may not be the only determining factor. MiRNAs, crucial regulators of post-transcriptional gene regulation could play a role in causing the observed differences in proliferation in these 2 expansion systems. The role of miRNA in NK cells biology is an emerging area of interest and their effect on regulation of protein expression and function during expansion of NK cells remain to be studied. We hypothesize that activating and expanding human NK cells on membrane bound IL15 and membrane bound IL21 wi…
author: Somanchi, Anitha
keywords: Natural Killer Cells, miRNA, IL21, IL15, NK cell expansion, Integrated data analysis, miR 124-3p, Bim, Stat 3, Tert, Biological Phenomena, Cell Phenomena, and Immunity, Immunology and Infectious Disease, Life Sciences, Medicine and Health Sciences, Oncology, Translational Medical Research
date published: 2017-12-01T08:00:00Z
date modified: 2026-07-24T05:48:59Z
provider: University of Texas Health Science Center at Houston
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Texas Health Science Center at Houston