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嵌合抗原受体自然杀伤细胞(CAR-NK细胞):是一种虚幻的希望还是一种有前景的疗法?

CAR-NK Cells: A Chimeric Hope or a Promising Therapy?

作者信息

Sabbah Mohamad, Jondreville Ludovic, Lacan Claire, Norol Francoise, Vieillard Vincent, Roos-Weil Damien, Nguyen Stéphanie

机构信息

Hematology Department, Pitie-Salpetriere Hospital, 75013 Paris, France.

Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm U1135, CNRS ERL 8255, 75013 Paris, France.

出版信息

Cancers (Basel). 2022 Aug 8;14(15):3839. doi: 10.3390/cancers14153839.


DOI:10.3390/cancers14153839
PMID:35954502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9367380/
Abstract

Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable quality and quantity of collected effector T cells, extended time of cell processing, limited number of available CAR cells, toxicities, and a high cost. Thanks to their powerful cytotoxic capabilities, with proven antitumor effects in both haploidentical hematopoietic stem cell transplantation and adoptive cell therapy against solid tumors and hematological malignancies, Natural Killer cells could be a promising alternative. Different sources of NK cells can be used, including cellular lines, cord blood, peripheral blood, and induced pluripotent stem cells. Their biggest advantage is the possibility of using them in an allogeneic context without major toxic side effects. However, the majority of the reports on CAR-NK cells concern preclinical or early clinical trials. Indeed, NK cells might be more difficult to engineer, and the optimization and standardization of expansion and transfection protocols need to be defined. Furthermore, their short persistence after infusion is also a major setback. However, with recent advances in manufacturing engineered CAR-NK cells exploiting their cytolytic capacities, antibody-dependent cellular cytotoxicity (ADCC), and cytokine production, "off-the-shelf" allogeneic CAR-NK cells can provide a great potential in cancer treatments.

摘要

嵌合抗原受体工程化T细胞(CAR-T)免疫疗法彻底改变了复发/难治性B细胞恶性肿瘤的治疗格局。尽管如此,自体T细胞的使用存在一定局限性,包括收集到的效应T细胞质量和数量参差不齐、细胞处理时间延长、可用的CAR细胞数量有限、毒性以及成本高昂。自然杀伤细胞凭借其强大的细胞毒性能力,在单倍体造血干细胞移植以及针对实体瘤和血液系统恶性肿瘤的过继性细胞治疗中均已证实具有抗肿瘤作用,可能是一种很有前景的替代方案。可使用不同来源的自然杀伤细胞,包括细胞系、脐带血、外周血和诱导多能干细胞。它们最大的优势在于有可能在同种异体环境中使用,且无重大毒副作用。然而,关于CAR-NK细胞的大多数报道都涉及临床前或早期临床试验。事实上,自然杀伤细胞可能更难进行工程改造,需要确定其扩增和转染方案的优化与标准化。此外,它们在输注后的短暂存活时间也是一个重大挫折。不过,随着利用自然杀伤细胞的细胞溶解能力、抗体依赖性细胞毒性(ADCC)和细胞因子产生来制造工程化CAR-NK细胞的技术取得了最新进展,“现货”型同种异体CAR-NK细胞在癌症治疗中具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/faa340d25417/cancers-14-03839-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/5d71d24cdf04/cancers-14-03839-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/046c72cfcc06/cancers-14-03839-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/a68ffa0d16db/cancers-14-03839-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/faa340d25417/cancers-14-03839-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/5d71d24cdf04/cancers-14-03839-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/046c72cfcc06/cancers-14-03839-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/a68ffa0d16db/cancers-14-03839-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0632/9367380/faa340d25417/cancers-14-03839-g004.jpg

相似文献

[1]
CAR-NK Cells: A Chimeric Hope or a Promising Therapy?

Cancers (Basel). 2022-8-8

[2]
[Allogeneic CAR-NK cells: A promising alternative to autologous CAR-T cells - State of the art, sources of NK cells, limits and perspectives].

Bull Cancer. 2021-10

[3]
CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies.

Stem Cell Res Ther. 2021-7-2

[4]
Anti-TIM3 chimeric antigen receptor-natural killer cells from engineered induced pluripotent stem cells effectively target acute myeloid leukemia cells.

Cancer Cell Int. 2023-11-27

[5]
CAR-NK cells from engineered pluripotent stem cells: Off-the-shelf therapeutics for all patients.

Stem Cells Transl Med. 2021-11

[6]
Natural killer cells: of-the-shelf cytotherapy for cancer immunosurveillance.

Am J Cancer Res. 2021-4-15

[7]
Engineering CAR-NK cells: how to tune innate killer cells for cancer immunotherapy.

Immunother Adv. 2022-2-3

[8]
Engineered human pluripotent stem cell-derived natural killer cells: the next frontier for cancer immunotherapy.

Blood Sci. 2019-9-17

[9]
[Current state and future prospects of off-the-shelf allogeneic CAR NK therapy].

Rinsho Ketsueki. 2024

[10]
Recent advances in chimeric antigen receptor natural killer cell therapy for overcoming intractable hematological malignancies.

Hematol Oncol. 2021-2

引用本文的文献

[1]
Tracing the development of CAR-T cell design: from concept to next-generation platforms.

Front Immunol. 2025-7-17

[2]
Multi-physiology modeling of the immune system in the era of precision immunotherapy.

Front Immunol. 2025-5-29

[3]
Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies.

J Hematol Oncol. 2025-5-19

[4]
Leukoreduction filter derived NK cells offer a promising source for off the shelf CAR NK cell immunotherapy.

Sci Rep. 2025-4-14

[5]
Developing CAR-T/NK cells that target EphA2 for non-small cell lung cancer treatment.

Front Immunol. 2025-3-13

[6]
Applications of mRNA Delivery in Cancer Immunotherapy.

Int J Nanomedicine. 2025-3-17

[7]
Application of adoptive cell therapy in malignant melanoma.

J Transl Med. 2025-1-22

[8]
The innate defenders: a review of natural killer cell immunotherapies in cancer.

Front Immunol. 2024-12-23

[9]
Engineering and targeting potential of CAR NK cells in colorectal cancer.

Chin Med J (Engl). 2024-11-5

[10]
The future of immunotherapy for diffuse large B-cell lymphoma.

Int J Cancer. 2025-1-15

本文引用的文献

[1]
Combined treatment with anti-PSMA CAR NK-92 cell and anti-PD-L1 monoclonal antibody enhances the antitumour efficacy against castration-resistant prostate cancer.

Clin Transl Med. 2022-6

[2]
Allogeneic double-negative CAR-T cells inhibit tumor growth without off-tumor toxicities.

Sci Immunol. 2022-4-22

[3]
NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma.

Blood Cancer J. 2021-8-14

[4]
Optimizing NK Cell-Based Immunotherapy in Myeloid Leukemia: Abrogating an Immunosuppressive Microenvironment.

Front Immunol. 2021

[5]
Systematic improvements in lentiviral transduction of primary human natural killer cells undergoing expansion.

Mol Ther Methods Clin Dev. 2021-1-20

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Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years.

Bone Marrow Transplant. 2021-7

[7]
Engineering NK Cells for CAR Therapy-Recent Advances in Gene Transfer Methodology.

Front Immunol. 2020

[8]
Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies.

Lancet. 2020-12-12

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Next-generation cell therapies: the emerging role of CAR-NK cells.

Hematology Am Soc Hematol Educ Program. 2020-12-4

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NK Cells in the Tumor Microenvironment.

Adv Exp Med Biol. 2020

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