Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy

Summary: Cell-based immunotherapy has become the new-generation cancer medicine, and “off-the-shelf” cell products that can be manufactured at large scale and distributed readily to treat patients are necessary. Invariant natural killer T (iNKT) cells are ideal cell carriers for developing allogenei...

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Autores principales:	Yan-Ruide Li, Yang Zhou, Yu Jeong Kim, Yanni Zhu, Feiyang Ma, Jiaji Yu, Yu-Chen Wang, Xianhui Chen, Zhe Li, Samuel Zeng, Xi Wang, Derek Lee, Josh Ku, Tasha Tsao, Christian Hardoy, Jie Huang, Donghui Cheng, Amélie Montel-Hagen, Christopher S. Seet, Gay M. Crooks, Sarah M. Larson, Joshua P. Sasine, Xiaoyan Wang, Matteo Pellegrini, Antoni Ribas, Donald B. Kohn, Owen Witte, Pin Wang, Lili Yang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	hematopoietic stem cell invariant natural killer T cells cancer immunotherapy allogeneic off-the-shelf cell therapy chimeric antigen receptor allogeneic HSC-engineered iNKT cells Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/64abb953f8fd44bf8d0230b66356f289
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spelling	oai:doaj.org-article:64abb953f8fd44bf8d0230b66356f2892021-11-18T04:52:16ZDevelopment of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy2666-379110.1016/j.xcrm.2021.100449https://doaj.org/article/64abb953f8fd44bf8d0230b66356f2892021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666379121003177https://doaj.org/toc/2666-3791Summary: Cell-based immunotherapy has become the new-generation cancer medicine, and “off-the-shelf” cell products that can be manufactured at large scale and distributed readily to treat patients are necessary. Invariant natural killer T (iNKT) cells are ideal cell carriers for developing allogeneic cell therapy because they are powerful immune cells targeting cancers without graft-versus-host disease (GvHD) risk. However, healthy donor blood contains extremely low numbers of endogenous iNKT cells. Here, by combining hematopoietic stem cell (HSC) gene engineering and in vitro differentiation, we generate human allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells at high yield and purity; these cells closely resemble endogenous iNKT cells, effectively target tumor cells using multiple mechanisms, and exhibit high safety and low immunogenicity. These cells can be further engineered with chimeric antigen receptor (CAR) to enhance tumor targeting or/and gene edited to ablate surface human leukocyte antigen (HLA) molecules and further reduce immunogenicity. Collectively, these preclinical studies demonstrate the feasibility and cancer therapy potential of AlloHSC-iNKT cell products and lay a foundation for their translational and clinical development.Yan-Ruide LiYang ZhouYu Jeong KimYanni ZhuFeiyang MaJiaji YuYu-Chen WangXianhui ChenZhe LiSamuel ZengXi WangDerek LeeJosh KuTasha TsaoChristian HardoyJie HuangDonghui ChengAmélie Montel-HagenChristopher S. SeetGay M. CrooksSarah M. LarsonJoshua P. SasineXiaoyan WangMatteo PellegriniAntoni RibasDonald B. KohnOwen WittePin WangLili YangElsevierarticlehematopoietic stem cellinvariant natural killer T cellscancer immunotherapyallogeneic off-the-shelf cell therapychimeric antigen receptorallogeneic HSC-engineered iNKT cellsMedicine (General)R5-920ENCell Reports Medicine, Vol 2, Iss 11, Pp 100449- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hematopoietic stem cell invariant natural killer T cells cancer immunotherapy allogeneic off-the-shelf cell therapy chimeric antigen receptor allogeneic HSC-engineered iNKT cells Medicine (General) R5-920
spellingShingle	hematopoietic stem cell invariant natural killer T cells cancer immunotherapy allogeneic off-the-shelf cell therapy chimeric antigen receptor allogeneic HSC-engineered iNKT cells Medicine (General) R5-920 Yan-Ruide Li Yang Zhou Yu Jeong Kim Yanni Zhu Feiyang Ma Jiaji Yu Yu-Chen Wang Xianhui Chen Zhe Li Samuel Zeng Xi Wang Derek Lee Josh Ku Tasha Tsao Christian Hardoy Jie Huang Donghui Cheng Amélie Montel-Hagen Christopher S. Seet Gay M. Crooks Sarah M. Larson Joshua P. Sasine Xiaoyan Wang Matteo Pellegrini Antoni Ribas Donald B. Kohn Owen Witte Pin Wang Lili Yang Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy
description	Summary: Cell-based immunotherapy has become the new-generation cancer medicine, and “off-the-shelf” cell products that can be manufactured at large scale and distributed readily to treat patients are necessary. Invariant natural killer T (iNKT) cells are ideal cell carriers for developing allogeneic cell therapy because they are powerful immune cells targeting cancers without graft-versus-host disease (GvHD) risk. However, healthy donor blood contains extremely low numbers of endogenous iNKT cells. Here, by combining hematopoietic stem cell (HSC) gene engineering and in vitro differentiation, we generate human allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells at high yield and purity; these cells closely resemble endogenous iNKT cells, effectively target tumor cells using multiple mechanisms, and exhibit high safety and low immunogenicity. These cells can be further engineered with chimeric antigen receptor (CAR) to enhance tumor targeting or/and gene edited to ablate surface human leukocyte antigen (HLA) molecules and further reduce immunogenicity. Collectively, these preclinical studies demonstrate the feasibility and cancer therapy potential of AlloHSC-iNKT cell products and lay a foundation for their translational and clinical development.
format	article
author	Yan-Ruide Li Yang Zhou Yu Jeong Kim Yanni Zhu Feiyang Ma Jiaji Yu Yu-Chen Wang Xianhui Chen Zhe Li Samuel Zeng Xi Wang Derek Lee Josh Ku Tasha Tsao Christian Hardoy Jie Huang Donghui Cheng Amélie Montel-Hagen Christopher S. Seet Gay M. Crooks Sarah M. Larson Joshua P. Sasine Xiaoyan Wang Matteo Pellegrini Antoni Ribas Donald B. Kohn Owen Witte Pin Wang Lili Yang
author_facet	Yan-Ruide Li Yang Zhou Yu Jeong Kim Yanni Zhu Feiyang Ma Jiaji Yu Yu-Chen Wang Xianhui Chen Zhe Li Samuel Zeng Xi Wang Derek Lee Josh Ku Tasha Tsao Christian Hardoy Jie Huang Donghui Cheng Amélie Montel-Hagen Christopher S. Seet Gay M. Crooks Sarah M. Larson Joshua P. Sasine Xiaoyan Wang Matteo Pellegrini Antoni Ribas Donald B. Kohn Owen Witte Pin Wang Lili Yang
author_sort	Yan-Ruide Li
title	Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy
title_short	Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy
title_full	Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy
title_fullStr	Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy
title_full_unstemmed	Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy
title_sort	development of allogeneic hsc-engineered inkt cells for off-the-shelf cancer immunotherapy
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/64abb953f8fd44bf8d0230b66356f289
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Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy

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