研究动态
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使用基于 Quantum pBac 的 CAR-T 工程系统制造 CD20/CD19 靶向 iCasp9 可调节 CAR-TSCM 细胞。

Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system.

发表日期:2024
作者: Peter S Chang, Yi-Chun Chen, Wei-Kai Hua, Jeff C Hsu, Jui-Cheng Tsai, Yi-Wun Huang, Yi-Hsin Kao, Pei-Hua Wu, Po-Nan Wang, Yi-Fang Chang, Ming-Chih Chang, Yu-Cheng Chang, Shiou-Ling Jian, Jiann-Shiun Lai, Ming-Tain Lai, Wei-Cheng Yang, Chia-Ning Shen, Kuo-Lan Karen Wen, Sareina Chiung-Yuan Wu
来源: Stem Cell Research & Therapy

摘要:

CD19 靶向嵌合抗原受体 (CAR) T 细胞疗法推动了复发/难治性 B 细胞恶性肿瘤治疗的范式转变。然而,超过 50% 的 CD19-CAR-T 治疗患者会出现疾病进展,这主要是由于抗原逃逸和低持续性。临床预后很大程度上受到 CAR-T 细胞功能和全身细胞因子毒性的影响。此外,高效、经济、持续地生产临床相关数量的病毒工程 CAR-T 细胞仍然是一个挑战。使用高效的基于piggyBac转座子的载体Quantum pBac™(qPB),我们开发了一种无病毒细胞工程系统,用于开发和生产多重CAR-T疗法。在这里,我们在体外和体内证明,使用 qPB™ 可以有效地生产一致、稳健和功能性的 CD20/CD19 双靶向 CAR-T 干细胞记忆 (CAR-TSCM) 细胞用于临床应用。特别是,我们表明,来自癌症患者的 qPB™ 制造的 CAR-T 细胞可以有效扩增,快速根除肿瘤,并且可以通过 iCasp9 自杀基因诱导药物安全地控制。因此,使用 qPB™ 系统简单地制造多重 CAR-T 细胞有可能提高疗效并扩大 CAR-T 疗法的可及性。版权所有:© 2024 Chang 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.