Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells

被引：0

作者：

Bo Wang

Shoichi Iriguchi

Masazumi Waseda

Norihiro Ueda

Tatsuki Ueda

Huaigeng Xu

Atsutaka Minagawa

Akihiro Ishikawa

Hisashi Yano

Tomoko Ishi

Ryoji Ito

Motohito Goto

Riichi Takahashi

Yasushi Uemura

Akitsu Hotta

Shin Kaneko

机构：

[1] Kyoto University,Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA)

[2] Kyoto University,Department of Clinical Application, CiRA

[3] Central Institute for Experimental Animals (CIEA),Humanized Model Laboratory

[4] National Cancer Center,Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center

[5] Kashiwa,undefined

来源：

Nature Biomedical Engineering | 2021年 / 5卷

关键词：

D O I：

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中图分类号：

学科分类号：

摘要：

Avoiding the immune rejection of transplanted T cells is central to the success of allogeneic cancer immunotherapies. One solution to protecting T-cell grafts from immune rejection involves the deletion of allogeneic factors and of factors that activate cytotoxic immune cells. Here we report the generation of hypoimmunogenic cancer-antigen-specific T cells derived from induced pluripotent stem cells (iPSCs) lacking β2-microglobulin, the class-II major histocompatibility complex (MHC) transactivator and the natural killer (NK) cell-ligand poliovirus receptor CD155, and expressing single-chain MHC class-I antigen E. In mouse models of CD20-expressing leukaemia or lymphoma, differentiated T cells expressing a CD20 chimeric antigen receptor largely escaped recognition by NKG2A+ and DNAM-1+ NK cells and by CD8 and CD4 T cells in the allogeneic recipients while maintaining anti-tumour potency. Hypoimmunogenic iPSC-derived T cells may contribute to the creation of off-the-shelf T cell immunotherapies.

引用

页码：429 / 440

页数：11

共 81 条

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