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同种异体 CAR 细胞疗法——不仅仅是一个白日梦。

Allogeneic CAR Cell Therapy-More Than a Pipe Dream.

机构信息

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, United States.

出版信息

Front Immunol. 2021 Jan 8;11:618427. doi: 10.3389/fimmu.2020.618427. eCollection 2020.


DOI:10.3389/fimmu.2020.618427
PMID:33488631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7821739/
Abstract

Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) has shown promise, particularly for the treatment of hematological malignancies. To date, the majority of clinically evaluated CAR cell products have been derived from autologous immune cells. While this strategy can be effective it also imposes several constraints regarding logistics. This includes i) availability of center to perform leukapheresis, ii) necessity for shipment to and from processing centers, and iii) time requirements for product manufacture and clinical release testing. In addition, previous cytotoxic therapies can negatively impact the effector function of autologous immune cells, which may then affect efficacy and/or durability of resultant CAR products. The use of allogeneic CAR cell products generated using cells from healthy donors has the potential to overcome many of these limitations, including through generation of "off the shelf" products. However, allogeneic CAR cell products come with their own challenges, including potential to induce graft-versus-host-disease, as well as risk of immune-mediated rejection by the host. Here we will review promises and challenges of allogeneic CAR immunotherapies, including those being investigated in preclinical models and/or early phase clinical studies.

摘要

采用表达嵌合抗原受体 (CAR) 的免疫细胞的过继细胞免疫疗法已显示出巨大的潜力,尤其是在治疗血液系统恶性肿瘤方面。迄今为止,大多数临床评估的 CAR 细胞产品均源自自体免疫细胞。虽然这种策略可能很有效,但它也对物流提出了一些限制。这包括:i)是否有中心进行白细胞分离,ii)是否需要运往和运离处理中心,以及 iii)产品制造和临床放行测试的时间要求。此外,以前的细胞毒性疗法可能会对自体免疫细胞的效应功能产生负面影响,这可能会影响由此产生的 CAR 产品的疗效和/或持久性。使用来自健康供体的细胞生成同种异体 CAR 细胞产品有可能克服许多这些限制,包括生成“现货”产品。然而,同种异体 CAR 细胞产品也带来了自身的挑战,包括引发移植物抗宿主病的可能性,以及宿主免疫介导排斥的风险。在这里,我们将综述同种异体 CAR 免疫疗法的前景和挑战,包括正在临床前模型和/或早期临床研究中进行的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aa8/7821739/9d089cd55f54/fimmu-11-618427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aa8/7821739/ac8658041fb4/fimmu-11-618427-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aa8/7821739/807645ec33f5/fimmu-11-618427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aa8/7821739/9d089cd55f54/fimmu-11-618427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aa8/7821739/ac8658041fb4/fimmu-11-618427-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aa8/7821739/807645ec33f5/fimmu-11-618427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aa8/7821739/9d089cd55f54/fimmu-11-618427-g003.jpg

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Allogeneic CART progress: platforms, current progress and limitations.

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[6]
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[7]
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[8]
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[9]
Allogeneic off-the-shelf CAR T-cell therapy for relapsed or refractory B-cell malignancies.

Blood Adv. 2025-4-8

[10]
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本文引用的文献

[1]
iPSC-derived NK cells maintain high cytotoxicity and enhance in vivo tumor control in concert with T cells and anti-PD-1 therapy.

Sci Transl Med. 2020-11-4

[2]
Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis.

Nat Med. 2020-11

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J Clin Oncol. 2020-11-10

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Endogenous TCR promotes in vivo persistence of CD19-CAR-T cells compared to a CRISPR/Cas9-mediated TCR knockout CAR.

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Genetic Ablation of HLA Class I, Class II, and the T-cell Receptor Enables Allogeneic T Cells to Be Used for Adoptive T-cell Therapy.

Cancer Immunol Res. 2020-7

[10]
CD4/CD8 T-Cell Selection Affects Chimeric Antigen Receptor (CAR) T-Cell Potency and Toxicity: Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial.

J Clin Oncol. 2020-6-10

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