piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells

Promising progress has been made in adoptive transfer of allogeneic natural killer (NK) cells to treat relapsed or refractory acute myeloid leukemia (AML). In this regard, chimeric antigen receptor (CAR)-modification of NK cells is considered as a compelling approach to augment the specificity and c...

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Autores principales:	Zhicheng Du, Yu Yang Ng, Shijun Zha, Shu Wang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	PiggyBac transposon NKG2D CAR-NK cells K562 APCs IL-15 acute myeloid leukemia Genetics QH426-470 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/3132fa6da25c405aa493feb06a356658
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spelling	oai:doaj.org-article:3132fa6da25c405aa493feb06a3566582021-11-22T04:26:38ZpiggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells2329-050110.1016/j.omtm.2021.10.014https://doaj.org/article/3132fa6da25c405aa493feb06a3566582021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2329050121001716https://doaj.org/toc/2329-0501Promising progress has been made in adoptive transfer of allogeneic natural killer (NK) cells to treat relapsed or refractory acute myeloid leukemia (AML). In this regard, chimeric antigen receptor (CAR)-modification of NK cells is considered as a compelling approach to augment the specificity and cytotoxicity of NK cells against AML. Using a non-viral piggyBac transposon technology and human peripheral blood-derived primary NK cells, we generated CAR-NK cells to target NKG2D ligands and demonstrated their in vitro activity in lysing cancer cells expressing the ligands and in vivo efficacy in inhibiting tumor growth in a xenograft KG-1 AML model. We further generated CAR-NK cells co-expressing transgenes for the NKG2D CAR and interleukin-15 (IL-15). The ectopic expression of IL-15 improved the in vitro and in vivo persistence of NKG2D CAR-NK cells, leading to enhanced in vivo tumor control and significant prolongation of mouse survival in the KG-1 AML model. Collectively, our findings demonstrate the ectopic expression of IL-15 as an important means to improve the antileukemic activity of NKG2D CAR-NK cells. Our study further illustrates the feasibility of using the piggyBac non-viral platform as an efficient and cost-effective way for CAR-NK cell manufacturing.Zhicheng DuYu Yang NgShijun ZhaShu WangElsevierarticlePiggyBac transposonNKG2D CAR-NK cellsK562 APCsIL-15acute myeloid leukemiaGeneticsQH426-470CytologyQH573-671ENMolecular Therapy: Methods & Clinical Development, Vol 23, Iss , Pp 582-596 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PiggyBac transposon NKG2D CAR-NK cells K562 APCs IL-15 acute myeloid leukemia Genetics QH426-470 Cytology QH573-671
spellingShingle	PiggyBac transposon NKG2D CAR-NK cells K562 APCs IL-15 acute myeloid leukemia Genetics QH426-470 Cytology QH573-671 Zhicheng Du Yu Yang Ng Shijun Zha Shu Wang piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells
description	Promising progress has been made in adoptive transfer of allogeneic natural killer (NK) cells to treat relapsed or refractory acute myeloid leukemia (AML). In this regard, chimeric antigen receptor (CAR)-modification of NK cells is considered as a compelling approach to augment the specificity and cytotoxicity of NK cells against AML. Using a non-viral piggyBac transposon technology and human peripheral blood-derived primary NK cells, we generated CAR-NK cells to target NKG2D ligands and demonstrated their in vitro activity in lysing cancer cells expressing the ligands and in vivo efficacy in inhibiting tumor growth in a xenograft KG-1 AML model. We further generated CAR-NK cells co-expressing transgenes for the NKG2D CAR and interleukin-15 (IL-15). The ectopic expression of IL-15 improved the in vitro and in vivo persistence of NKG2D CAR-NK cells, leading to enhanced in vivo tumor control and significant prolongation of mouse survival in the KG-1 AML model. Collectively, our findings demonstrate the ectopic expression of IL-15 as an important means to improve the antileukemic activity of NKG2D CAR-NK cells. Our study further illustrates the feasibility of using the piggyBac non-viral platform as an efficient and cost-effective way for CAR-NK cell manufacturing.
format	article
author	Zhicheng Du Yu Yang Ng Shijun Zha Shu Wang
author_facet	Zhicheng Du Yu Yang Ng Shijun Zha Shu Wang
author_sort	Zhicheng Du
title	piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells
title_short	piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells
title_full	piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells
title_fullStr	piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells
title_full_unstemmed	piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells
title_sort	piggybac system to co-express nkg2d car and il-15 to augment the in vivo persistence and anti-aml activity of human peripheral blood nk cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/3132fa6da25c405aa493feb06a356658
work_keys_str_mv	AT zhichengdu piggybacsystemtocoexpressnkg2dcarandil15toaugmenttheinvivopersistenceandantiamlactivityofhumanperipheralbloodnkcells AT yuyangng piggybacsystemtocoexpressnkg2dcarandil15toaugmenttheinvivopersistenceandantiamlactivityofhumanperipheralbloodnkcells AT shijunzha piggybacsystemtocoexpressnkg2dcarandil15toaugmenttheinvivopersistenceandantiamlactivityofhumanperipheralbloodnkcells AT shuwang piggybacsystemtocoexpressnkg2dcarandil15toaugmenttheinvivopersistenceandantiamlactivityofhumanperipheralbloodnkcells
_version_	1718418213926076416

piggyBac system to co-express NKG2D CAR and IL-15 to augment the in vivo persistence and anti-AML activity of human peripheral blood NK cells

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