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现成的免疫疗法:多能干细胞衍生免疫细胞的生成和应用。

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

机构信息

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, China.

出版信息

Cell Prolif. 2023 Apr;56(4):e13425. doi: 10.1111/cpr.13425. Epub 2023 Mar 1.


DOI:10.1111/cpr.13425
PMID:36855955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10068955/
Abstract

In recent years, great strides have been made toward the development of immune cell-based therapies in the treatment of refractory malignancies. Primary T cells and NK cells armed with chimeric antigen receptors have achieved tremendous clinical success especially in patients with leukaemia and lymphoma. However, the autologous origin of these effector cells means that a single batch of laboriously engineered cells treats only a certain patient, leading to high cost, ununiform product quality, and risk of delay in treatment, and therefore results in restricted accessibility of these therapies to the overwhelming majority of the patients. Addressing these tricky obstacles calls for the development of universal immune cell products that can be provided 'off the shelf' in a large amount. Pluripotent stem cells (PSCs), owing to their unique capacity of self-renewal and the potential of multi-lineage differentiation, offer an unlimited cell source to generate uniform and scalable engineered immune cells. This review discusses the major advances in the development of PSC-derived immune cell differentiation approaches and their therapeutic potential in treating both hematologic malignancies and solid tumours. We also consider the potency of PSC-derived immune cells as an alternative therapeutic strategy for other diseases, such as autoimmune diseases, fibrosis, infections, et al.

摘要

近年来,在开发基于免疫细胞的疗法以治疗难治性恶性肿瘤方面取得了重大进展。嵌合抗原受体修饰的原代 T 细胞和 NK 细胞已取得巨大的临床成功,尤其是在白血病和淋巴瘤患者中。然而,这些效应细胞的自体起源意味着每一批精心设计的细胞仅能治疗特定的患者,这导致了成本高、产品质量不均一以及治疗延误的风险,从而限制了这些疗法在绝大多数患者中的可及性。为了解决这些棘手的障碍,需要开发能够大量“现货供应”的通用免疫细胞产品。多能干细胞(PSCs)由于其自我更新的独特能力和多能分化的潜力,为生成均匀且可扩展的工程化免疫细胞提供了无限的细胞来源。本综述讨论了 PSC 衍生的免疫细胞分化方法的主要进展及其在治疗血液系统恶性肿瘤和实体瘤方面的治疗潜力。我们还考虑了 PSC 衍生的免疫细胞作为治疗其他疾病(如自身免疫性疾病、纤维化、感染等)的替代治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b04f/10068955/bf929876e0e6/CPR-56-e13425-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b04f/10068955/bf929876e0e6/CPR-56-e13425-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b04f/10068955/bf929876e0e6/CPR-56-e13425-g002.jpg

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

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本文引用的文献

[1]
Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells.

Cell Discov. 2022-11-8

[2]
Engineered and banked iPSCs for advanced NK- and T-cell immunotherapies.

Blood. 2023-2-23

[3]
DLL4 and VCAM1 enhance the emergence of T cell-competent hematopoietic progenitors from human pluripotent stem cells.

Sci Adv. 2022-8-26

[4]
Human pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection.

Stem Cell Reports. 2022-9-13

[5]
EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity.

Cell Stem Cell. 2022-8-4

[6]
Single transcription factor efficiently leads human induced pluripotent stem cells to functional microglia.

Inflamm Regen. 2022-7-1

[7]
Macrophages derived from pluripotent stem cells: prospective applications and research gaps.

Cell Biosci. 2022-6-20

[8]
Cost-Effectiveness of Chimeric Antigen Receptor T Cell Therapy in Patients with Relapsed or Refractory Large B Cell Lymphoma: No Impact of Site of Care.

Adv Ther. 2022-8

[9]
Induced Pluripotent Stem Cell-Derived Monocytes/Macrophages in Autoinflammatory Diseases.

Front Immunol. 2022

[10]
Emerging NK cell therapies for cancer and the promise of next generation engineering of iPSC-derived NK cells.

J Immunother Cancer. 2022-5

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