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迈向免疫基因 T 细胞治疗的精准制造。

Toward precision manufacturing of immunogene T-cell therapies.

机构信息

Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Cytotherapy. 2018 May;20(5):623-638. doi: 10.1016/j.jcyt.2017.12.007. Epub 2018 Apr 10.

Abstract

Cancer can be effectively targeted using a patient's own T cells equipped with synthetic receptors, including chimeric antigen receptors (CARs) that redirect and reprogram these lymphocytes to mediate tumor rejection. Over the past two decades, several strategies to manufacture genetically engineered T cells have been proposed, with the goal of generating optimally functional cellular products for adoptive transfer. Based on this work, protocols for manufacturing clinical-grade CAR T cells have been established, but these complex methods have been used to treat only a few hundred individuals. As CAR T-cell therapy progresses into later-phase clinical trials and becomes an option for more patients, a major consideration for academic institutions and industry is developing robust manufacturing processes that will permit scaling-out production of immunogene T-cell therapies in a reproducible and efficient manner. In this review, we will discuss the steps involved in cell processing, the major obstacles surrounding T-cell manufacturing platforms and the approaches for improving cellular product potency. Finally, we will address the challenges of expanding CAR T-cell therapy to a global patient population.

摘要

可以使用配备合成受体的患者自身 T 细胞(包括嵌合抗原受体 (CAR))来有效靶向癌症,这些受体可重新定向和重新编程这些淋巴细胞以介导肿瘤排斥。在过去的二十年中,已经提出了几种制造基因工程 T 细胞的策略,其目的是生成用于过继转移的最佳功能细胞产物。在此基础上,已经建立了用于制造临床级 CAR T 细胞的方案,但这些复杂的方法仅用于治疗几百人。随着 CAR T 细胞疗法进入后期临床试验并成为更多患者的选择,学术界和工业界的一个主要考虑因素是开发强大的制造工艺,以便以可重复且有效的方式大规模生产免疫基因 T 细胞疗法。在这篇综述中,我们将讨论细胞处理涉及的步骤、T 细胞制造平台周围的主要障碍以及提高细胞产品效力的方法。最后,我们将讨论将 CAR T 细胞疗法扩展到全球患者群体的挑战。

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