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扩大规模:工程化 T 细胞疗法制造的进展与挑战。

Scaling up and scaling out: Advances and challenges in manufacturing engineered T cell therapies.

机构信息

National Institutes of Health, Clinical Center, Center for Cellular Engineering, Bethesda, USA.

出版信息

Int Rev Immunol. 2022;41(6):638-648. doi: 10.1080/08830185.2022.2067154. Epub 2022 Apr 29.


DOI:10.1080/08830185.2022.2067154
PMID:35486592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9815724/
Abstract

Engineered T cell therapies such as CAR-T cells and TCR-T cells have generated impressive patient responses in previously incurable diseases. In the past few years there have been a number of technical innovations that enable robust clinical manufacturing in functionally closed and often automated systems. Here we describe the latest technology used to manufacture CAR- and TCR-engineered T cells in the clinic, including cell purification, transduction/transfection, expansion and harvest. To help compare the different systems available, we present three case studies of engineered T cells manufactured for phase I clinical trials at the NIH Clinical Center (CD30 CAR-T cells for lymphoma, CD19/CD22 bispecific CAR-T cells for B cell malignancies, and E7 TCR T cells for human papilloma virus-associated cancers). Continued improvement in cell manufacturing technology will help enable world-wide implementation of engineered T cell therapies.

摘要

工程化 T 细胞疗法,如 CAR-T 细胞和 TCR-T 细胞,在以前无法治愈的疾病中产生了令人印象深刻的患者应答。在过去的几年中,出现了许多技术创新,使功能封闭且通常自动化的系统能够进行强大的临床制造。在这里,我们描述了用于在临床上制造 CAR 和 TCR 工程化 T 细胞的最新技术,包括细胞纯化、转导/转染、扩增和收获。为了帮助比较可用的不同系统,我们展示了在 NIH 临床中心进行的 I 期临床试验中制造的三种工程化 T 细胞的案例研究(淋巴瘤用的 CD30 CAR-T 细胞、B 细胞恶性肿瘤用的 CD19/CD22 双特异性 CAR-T 细胞和人乳头瘤病毒相关癌症用的 E7 TCR T 细胞)。细胞制造技术的持续改进将有助于在全球范围内实施工程化 T 细胞疗法。

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本文引用的文献

[1]
Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma.

Cancer Res Commun. 2023-5

[2]
High efficiency closed-system gene transfer using automated spinoculation.

J Transl Med. 2021-11-24

[3]
Scalable Manufacturing of CAR T cells for Cancer Immunotherapy.

Blood Cancer Discov. 2021-9

[4]
CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial.

Nat Med. 2021-8

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Single-cell multiomics dissection of basal and antigen-specific activation states of CD19-targeted CAR T cells.

J Immunother Cancer. 2021-5

[6]
Global Perspective on the Development of Genetically Modified Immune Cells for Cancer Therapy.

Front Immunol. 2021-2-15

[7]
TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers.

Nat Med. 2021-3

[8]
Insight into next-generation CAR therapeutics: designing CAR T cells to improve clinical outcomes.

J Clin Invest. 2021-1-19

[9]
Design and Assessment of Novel Anti-CD30 Chimeric Antigen Receptors with Human Antigen-Recognition Domains.

Hum Gene Ther. 2021-7

[10]
Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial.

Nat Med. 2020-10-5

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