Abstract
The generation of immune cells from human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) has been of keen interest to regenerative medicine. Pluripotent stem cell-derived immune cells such as natural killer cells, macrophages, and lymphoid cells, especially T cells, can be used in immune cell therapy to treat incurable cancers. Moreover, since the advent of chimeric antigen receptor (CAR) technology, the success of CAR-T cells in the clinic has galvanized new efforts to harness the power of CAR technology to generate CAR-engineered immune cells from pluripotent stem cells. This review provides a summary of pluripotent stem cell-derived immune cells and CAR technology, together with perspectives on combining pluripotent stem-cell derived immune cells and CAR engineering to pave a new way for developing next generation immune cell therapy.
Highlights
Human pluripotent stem cells—embryonic stem cells (ES cells) and induced pluripotent stem cells—are cell types that can theoretically give rise to all of the cells of our body and proliferate indefinitely, providing an inexhaustible source for immune cell generation [1]
This review will summarize the derivation of immune cells [natural killer (NK) cells, macrophages, and T cells] from human pluripotent stem cells, and will provide perspectives on combining pluripotent stem-cell derived immune cells, gene editing, and Chimeric antigen receptor (CAR) engineering to pave a new way for developing generation immune cell therapy
clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 tools provide a simple means of generating multiplex gene modifications, and to date 11 clinical trials for gene-edited CAR-T cells have been registered [83]
Summary
Human pluripotent stem cells—embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells)—are cell types that can theoretically give rise to all of the cells of our body and proliferate indefinitely, providing an inexhaustible source for immune cell generation [1]. Primary immune cells are refractory to gene editing procedures and such cells have limited proliferation activity, which hinders clonal selection. With their capacity for indefinite proliferation and their pluripotent character, human pluripotent stem cells could be a perfect alternative for generating an unlimited number of improved immune cells through gene modification and clonal selection [6]. This review will summarize the derivation of immune cells [natural killer (NK) cells, macrophages, and T cells] from human pluripotent stem cells, and will provide perspectives on combining pluripotent stem-cell derived immune cells, gene editing, and CAR engineering to pave a new way for developing generation immune cell therapy
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