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嵌合抗原受体自然杀伤细胞在血液系统恶性肿瘤治疗中的新兴作用。

Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies.

作者信息

Testa Ugo, Castelli Germana, Pelosi Elvira

机构信息

Department of Oncology, Istituto Superiore di Sanità, 00135 Rome, Italy.

出版信息

Cancers (Basel). 2025 Apr 26;17(9):1454. doi: 10.3390/cancers17091454.

DOI:10.3390/cancers17091454
PMID:40361380
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12071031/
Abstract

The clinical use of T lymphocytes engineered with chimeric antigen receptors (CARs) has revolutionized the treatment of patients with refractory or relapsed hematological malignancies. CAR natural killer (CAR-NK) cells are NK cells engineered with CARs to specifically target cell antigens expressed on the membrane of tumor cells. CAR-NK cells could offer some advantages with respect to CAR-T cells, related to their specific and innate anti-tumor activity, availability as an "off the shelf" cellular therapy, reduced costs, and improved safety. Promising efficacy of CAR-Nk cell therapy was observed in clinical trials based on the treatment of some hematological malignancies. However, to date, the clinical experience of CAR-NK cell therapy has been preliminary, with the evaluation of only a limited number of patients. Furthermore, CAR-NK cell therapy has been limited by the short persistence of these cells and by the suboptimal cytotoxic activity of some CAR-NK preparations. Therefore, studies based on the enrollment of a number of patients is required to carefully assess and confirm the safety and the efficacy of CAR-NK cell therapy in hematological malignancies and to compare their efficacy with respect to allogeneic CAR-T cells.

摘要

嵌合抗原受体(CAR)工程化改造的T淋巴细胞在临床上的应用彻底改变了难治性或复发性血液系统恶性肿瘤患者的治疗方式。CAR自然杀伤(CAR-NK)细胞是经CAR工程化改造的NK细胞,可特异性靶向肿瘤细胞膜上表达的细胞抗原。与CAR-T细胞相比,CAR-NK细胞具有一些优势,包括其特异性和天然抗肿瘤活性、可作为“现货”细胞疗法使用、成本降低以及安全性提高。在基于某些血液系统恶性肿瘤治疗的临床试验中观察到了CAR-NK细胞疗法有前景的疗效。然而,迄今为止,CAR-NK细胞疗法的临床经验还很初步,仅评估了有限数量的患者。此外,CAR-NK细胞疗法受到这些细胞持续时间短以及某些CAR-NK制剂细胞毒性活性欠佳的限制。因此,需要开展基于大量患者入组的研究,以仔细评估和确认CAR-NK细胞疗法在血液系统恶性肿瘤中的安全性和疗效,并将其疗效与同种异体CAR-T细胞进行比较。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc25/12071031/03a52e04b962/cancers-17-01454-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc25/12071031/03a52e04b962/cancers-17-01454-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc25/12071031/03a52e04b962/cancers-17-01454-g001.jpg

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Cytotherapy. 2025 Feb 24. doi: 10.1016/j.jcyt.2025.02.006.
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Feeder-cell-free system for production of natural killer cells from cord blood hematopoietic stem and progenitor cells.用于从脐带血造血干细胞和祖细胞生产自然杀伤细胞的无饲养细胞系统。
Front Immunol. 2025 Feb 20;16:1531736. doi: 10.3389/fimmu.2025.1531736. eCollection 2025.
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Nat Commun. 2025 Feb 1;16(1):1248. doi: 10.1038/s41467-025-56270-6.
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Lancet. 2025 Jan 11;405(10473):127-136. doi: 10.1016/S0140-6736(24)02462-0.
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