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《细胞治疗和基因治疗的产业化:临床转化面临的挑战》

Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation.

机构信息

Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea.

Cell and Gene Therapy Institute (CGTI), Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.

出版信息

Ann Lab Med. 2024 Jul 1;44(4):314-323. doi: 10.3343/alm.2023.0382. Epub 2024 Feb 16.


DOI:10.3343/alm.2023.0382
PMID:38361427
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10961620/
Abstract

The safety and efficacy of both cell and gene therapies have been demonstrated in numerous preclinical and clinical trials. Chimeric antigen receptor T (CAR-T) cell therapy, which leverages the technologies of both cell and gene therapies, has also shown great promise for treating various cancers. Advancements in pertinent fields have also highlighted challenges faced while manufacturing cell and gene therapy products. Potential problems and obstacles must be addressed to ease the clinical translation of individual therapies. Literature reviews of representative cell-based, gene-based, and cell-based gene therapies with regard to their general manufacturing processes, the challenges faced during manufacturing, and QC specifications are limited. We review the general manufacturing processes of cell and gene therapies, including those involving mesenchymal stem cells, viral vectors, and CAR-T cells. The complexities associated with the manufacturing processes and subsequent QC/validation processes may present challenges that could impede the clinical progression of the products. This article addresses these potential challenges. Further, we discuss the use of the manufacturing model and its impact on cell and gene therapy.

摘要

细胞和基因治疗的安全性和有效性已在众多临床前和临床试验中得到证实。嵌合抗原受体 T(CAR-T)细胞疗法利用了细胞和基因治疗的技术,也为治疗各种癌症带来了巨大的希望。相关领域的进展也凸显了制造细胞和基因治疗产品所面临的挑战。为了促进个体化治疗的临床转化,必须解决潜在的问题和障碍。关于代表性的基于细胞、基于基因和基于细胞基因治疗的文献综述,涉及它们的一般制造工艺、制造过程中面临的挑战以及 QC 规范,受到了限制。我们综述了细胞和基因治疗的一般制造工艺,包括涉及间充质干细胞、病毒载体和 CAR-T 细胞的制造工艺。制造工艺和随后的 QC/验证工艺的复杂性可能带来挑战,从而阻碍产品的临床进展。本文讨论了这些潜在的挑战。此外,我们还讨论了制造模型的使用及其对细胞和基因治疗的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afed/10961620/51e729fb7101/alm-44-4-314-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afed/10961620/51e729fb7101/alm-44-4-314-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afed/10961620/51e729fb7101/alm-44-4-314-f1.jpg

相似文献

[1]
Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation.

Ann Lab Med. 2024-7-1

[2]
Choosing the Right Tool for Genetic Engineering: Clinical Lessons from Chimeric Antigen Receptor-T Cells.

Hum Gene Ther. 2021-10

[3]
Strategies for manufacturing cell therapy products aligned with patient needs.

Methods Cell Biol. 2022

[4]
Overcoming Challenges in Process Development of Cellular Therapies.

Curr Hematol Malig Rep. 2019-8

[5]
Chimeric antigen receptor-T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods.

Cytotherapy. 2019-2-13

[6]
Chimeric antigen receptor-engineered T-cell therapy for liver cancer.

Hepatobiliary Pancreat Dis Int. 2018-5-24

[7]
Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives.

Viruses. 2021-8-2

[8]
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Mol Ther. 2019-4-8

[9]
Taking Lessons from CAR-T Cells and Going Beyond: Tailoring Design and Signaling for CAR-NK Cells in Cancer Therapy.

Front Immunol. 2022

[10]
Better by design: What to expect from novel CAR-engineered cell therapies?

Biotechnol Adv. 2022-9

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[1]
Unconventional Immunotherapies in Cancer: Opportunities and Challenges.

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[2]
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[3]
Two promising approaches in the treatment of myocardial infarction: stem cells and gene therapy.

Front Cardiovasc Med. 2025-2-19

[4]
GMP manufacturing of cell and gene therapy products: Challenges, opportunities, and pathways forward.

Mol Ther. 2025-5-7

[5]
As new cell and gene therapies emerge from academia, we must RISE to the opportunity.

Nat Biotechnol. 2025-1

[6]
Gene therapy and kidney diseases.

Mol Ther Methods Clin Dev. 2024-9-6

[7]
Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions.

Signal Transduct Target Ther. 2024-7-1

[8]
Towards a Cure for Diamond-Blackfan Anemia: Views on Gene Therapy.

Cells. 2024-5-27

本文引用的文献

[1]
Strategies for overcoming bottlenecks in allogeneic CAR-T cell therapy.

Front Immunol. 2023

[2]
A new T-antigen negative HEK293 cell line with improved AAV productivity.

Biotechnol Bioeng. 2023-7

[3]
Clinical applications of gene therapy for rare diseases: A review.

Int J Exp Pathol. 2023-8

[4]
Critical challenges and advances in recombinant adeno-associated virus (rAAV) biomanufacturing.

Biotechnol Bioeng. 2023-9

[5]
Large-scale purification of functional AAV particles packaging the full genome using short-term ultracentrifugation with a zonal rotor.

Gene Ther. 2023-8

[6]
Current good manufacturing practice considerations for mesenchymal stromal cells as therapeutic agents.

Biomater Biosyst. 2021-5-5

[7]
AAV vectors applied to the treatment of CNS disorders: Clinical status and challenges.

J Control Release. 2023-3

[8]
Lentiviral vector gene therapies come of age with two FDA approvals.

Nat Rev Drug Discov. 2022-11

[9]
Chimeric Antigen Receptor T-Cell Therapies: Barriers and Solutions to Access.

JCO Oncol Pract. 2022-12

[10]
Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome.

Front Immunol. 2022

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