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嵌合抗原受体T细胞(CAR-T)疗法生产的经济高效策略。

Cost-effective strategies for CAR-T cell therapy manufacturing.

作者信息

Abdo Luiza, Batista-Silva Leonardo Ribeiro, Bonamino Martín Hernán

机构信息

Cell and Gene Therapy Program, Research Coordination, National Cancer Institute (INCA), Rio de Janeiro 20231-050, Brazil.

Vice-Presidency of Research and Biological Collections (VPPCB), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil.

出版信息

Mol Ther Oncol. 2025 Apr 3;33(2):200980. doi: 10.1016/j.omton.2025.200980. eCollection 2025 Jun 18.

Abstract

CAR-T cell therapy has revolutionized cancer treatment, with approvals for conditions like acute B-leukemia, large B cell lymphoma (LBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and multiple myeloma. However, its high costs limit accessibility. Key factors driving these costs include the need for personalized, autologous treatments, transportation to specialized facilities, reliance on viral vectors requiring advanced laboratories, and lengthy cell expansion processes. To address these challenges, alternative strategies aim to simplify and reduce production complexity. Non-viral vectors, such as Sleeping Beauty, piggyBac, and CRISPR, delivered via nanoparticles or electroporation, present promising solutions. These methods could streamline manufacturing, eliminate the need for viral vectors, and reduce associated costs. Furthermore, shortening cell expansion periods and optimizing protocols could significantly accelerate production. An emerging approach involves using genetically edited T cells from healthy donors to create universal CAR-T products capable of treating multiple patients. Finally, decentralized point-of-care (POC) manufacturing of CAR-T cells minimize logistical expenses, eliminating the need for complex infrastructure, and enabling localized production closer to patients. This innovative strategy holds potential for broadening access and reducing costs, representing a step toward democratizing CAR-T therapy. Combined, these advances could make this groundbreaking treatment more feasible for healthcare systems worldwide.

摘要

嵌合抗原受体T细胞(CAR-T)疗法彻底改变了癌症治疗方式,已获批用于治疗急性B淋巴细胞白血病、大B细胞淋巴瘤(LBCL)、滤泡性淋巴瘤(FL)、套细胞淋巴瘤(MCL)和多发性骨髓瘤等病症。然而,其高昂的成本限制了可及性。推动这些成本的关键因素包括对个性化自体治疗的需求、前往专业机构的交通费用、对需要先进实验室的病毒载体的依赖以及漫长的细胞扩增过程。为应对这些挑战,替代策略旨在简化并降低生产复杂性。通过纳米颗粒或电穿孔递送的非病毒载体,如睡美人转座子、猪尾巴转座子和CRISPR,提供了有前景的解决方案。这些方法可以简化生产流程,消除对病毒载体的需求,并降低相关成本。此外,缩短细胞扩增周期并优化方案可显著加快生产速度。一种新兴方法是使用来自健康供体的基因编辑T细胞来创建能够治疗多名患者的通用CAR-T产品。最后,CAR-T细胞的分散式即时护理(POC)制造可将后勤费用降至最低,无需复杂的基础设施,并能够在更靠近患者的地方进行本地化生产。这种创新策略具有扩大可及性和降低成本的潜力,代表着CAR-T疗法走向普及的一步。综合起来,这些进展可能使这种开创性的治疗方法在全球医疗系统中更可行。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be3/12022644/638b22bc0bfc/fx1.jpg

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