T cells modified to express intelligently designed chimeric antigen receptors (CARs) are exceptionally powerful therapeutic agents for relapsed and refractory blood cancers and have the potential to revolutionize therapy for many other diseases. To circumvent the complexity and cost associated with broad-scale implementation of manufactured adoptive cell therapy products, alternative strategies to generate CAR T cells by direct infusion of nanoparticle-formulated nucleic acids or engineered viral vectors under development have received a great deal of attention in the past few years. Here, we outline the manufacturing process as a motivating framework for direct strategies and discuss emerging data from preclinical models to highlight the potency of the approach, the applicability for new disease indications, and the remaining challenges associated with clinical readiness, including delivery specificity, long term efficacy, and safety.

中文翻译：

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直接体内 CAR T 细胞工程

经修饰可表达智能设计的嵌合抗原受体 (CAR) 的 T 细胞是治疗复发性和难治性血癌的极其强大的治疗剂，并有可能彻底改变许多其他疾病的治疗。为了规避大规模实施制造的过继细胞治疗产品所带来的复杂性和成本，通过直接输注纳米颗粒配制的核酸或正在开发的工程病毒载体来产生 CAR T 细胞的替代策略已受到业界的广泛关注。过去几年。在这里，我们将制造过程概述为直接策略的激励框架，并讨论来自临床前模型的新数据，以强调该方法的效力、新疾病适应症的适用性以及与临床准备相关的剩余挑战，包括交付特异性、长期长期疗效和安全性。