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基于多能干细胞的免疫疗法:转化研究、细胞分化和基因修饰的进展

Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications.

作者信息

Lei Qi, Deng Hongkui, Sun Shicheng

机构信息

Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking University Health Science Center, Beijing 100191, China.

Changping Laboratory, Beijing 102206, China.

出版信息

Life Med. 2025 Jan 18;4(1):lnaf002. doi: 10.1093/lifemedi/lnaf002. eCollection 2025 Feb.


DOI:10.1093/lifemedi/lnaf002
PMID:40110110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11916900/
Abstract

Cell-based immunotherapy, recognized as living drugs, is revolutionizing clinical treatment to advanced cancer and shaping the landscape of biomedical research for complex diseases. The differentiation of human pluripotent stem cells (PSCs) emerges as a novel platform with the potential to generate an unlimited supply of therapeutic immune cells, especially when coupled with gene modification techniques. PSC-based immunotherapy is expected to meet the vast clinical demand for living drugs. Here, we examine recent preclinical and clinical advances in PSC-based immunotherapy, focusing on PSC gene modification strategies and differentiation methods for producing therapeutic immune cells. We also discuss opportunities in this field and challenges in cell quality and safety and stresses the need for further research and transparency to unlock the full potential of PSC immunotherapies.

摘要

基于细胞的免疫疗法被视为“活药物”,正在彻底改变晚期癌症的临床治疗,并塑造复杂疾病生物医学研究的格局。人类多能干细胞(PSC)的分化成为一个新平台,有潜力产生无限量的治疗性免疫细胞,特别是与基因编辑技术相结合时。基于PSC的免疫疗法有望满足对“活药物”的巨大临床需求。在这里,我们研究了基于PSC的免疫疗法的最新临床前和临床进展,重点关注用于产生治疗性免疫细胞的PSC基因编辑策略和分化方法。我们还讨论了该领域的机遇以及细胞质量和安全性方面的挑战,并强调需要进一步研究和提高透明度,以充分发挥PSC免疫疗法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/36da13716382/lnaf002_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/78b67085712e/lnaf002_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/a38bf3d2dee3/lnaf002_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/6d4200b05bbd/lnaf002_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/36da13716382/lnaf002_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/78b67085712e/lnaf002_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/a38bf3d2dee3/lnaf002_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/6d4200b05bbd/lnaf002_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f0/11916900/36da13716382/lnaf002_fig4.jpg

相似文献

[1]
Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications.

Life Med. 2025-1-18

[2]
Developing enhanced immunotherapy using NKG2A knockout human pluripotent stem cell-derived NK cells.

Cell Rep. 2024-11-26

[3]
Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.

Cells Tissues Organs. 2023

[4]
'Off the shelf' immunotherapies: Generation and application of pluripotent stem cell-derived immune cells.

Cell Prolif. 2023-4

[5]
Unlocking the potential of iPSC-derived immune cells: engineering iNK and iT cells for cutting-edge immunotherapy.

Front Immunol. 2024-8-30

[6]
CAR-NK cells from engineered pluripotent stem cells: Off-the-shelf therapeutics for all patients.

Stem Cells Transl Med. 2021-11

[7]
From pluripotent stem cells to T cells.

Exp Hematol. 2019-3

[8]
Differentiation of pluripotent stem cells for regenerative medicine.

Biochem Biophys Res Commun. 2016-2-26

[9]
Generation and clinical potential of functional T lymphocytes from gene-edited pluripotent stem cells.

Exp Hematol Oncol. 2022-5-14

[10]
Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies.

Nat Med. 2013-8-6

引用本文的文献

[1]
Global clinical trials on stem cell therapy for autoimmune diseases: trends and future directions.

Front Immunol. 2025-7-24

[2]
Gene therapy strategies for aging intervention.

Cell Insight. 2025-5-23

本文引用的文献

[1]
TCR cell therapies vanquish solid tumors - finally.

Nat Biotechnol. 2024-10

[2]
Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis.

Nat Commun. 2024-9-4

[3]
Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells.

Nat Biotechnol. 2024-9-2

[4]
Generation of dual-attribute iTNK cells from hPSCs for cancer immunotherapy.

Cell Rep Methods. 2024-9-16

[5]
Human iPSC-derived CD4 Treg-like cells engineered with chimeric antigen receptors control GvHD in a xenograft model.

Cell Stem Cell. 2024-6-6

[6]
Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Nat Biotechnol. 2025-3

[7]
Activating innate immune responses repolarizes hPSC-derived CAR macrophages to improve anti-tumor activity.

Cell Stem Cell. 2024-7-5

[8]
Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer.

Cell Stem Cell. 2024-6-6

[9]
FOXO1 is a master regulator of memory programming in CAR T cells.

Nature. 2024-5

[10]
FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy.

Nature. 2024-5

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