Adoptive T cell transfer has shown great success in treating blood cancers, resulting in a growing number of FDA-approved therapies using chimeric antigen receptor (CAR)-engineered T cells. However, the effectiveness of this treatment for solid tumors is still not satisfactory, emphasizing the need for improved T cell engineering strategies and combination approaches. Currently, CAR T cells are mainly manufactured using gammaretroviral and lentiviral vectors due to their high transduction efficiency. However, there are concerns about their safety, the high cost of producing them in compliance with current Good Manufacturing Practices (cGMP), regulatory obstacles, and limited cargo capacity, which limit the broader use of engineered T cell therapies. To overcome these limitations, researchers have explored non-viral approaches, such as membrane permeabilization and carrier-mediated methods, as more versatile and sustainable alternatives for next-generation T cell engineering. Non-viral delivery methods can be designed to transport a wide range of molecules, including RNA, which allows for more controlled and safe modulation of T cell phenotype and function. In this review, we provide an overview of non-viral RNA delivery in adoptive T cell therapy. We first define the different types of RNA therapeutics, highlighting recent advancements in manufacturing for their therapeutic use. We then discuss the challenges associated with achieving effective RNA delivery in T cells. Next, we provide an overview of current and emerging technologies for delivering RNA into T cells. Finally, we discuss ongoing preclinical and clinical studies involving RNA-modified T cells.

中文翻译：

---

用于治疗性 T 细胞工程的 RNA 非病毒递送

过继性 T 细胞移植在治疗血癌方面取得了巨大成功，导致越来越多的 FDA 批准使用嵌合抗原受体 (CAR) 工程 T 细胞的疗法。然而，这种治疗实体瘤的效果仍然不能令人满意，强调需要改进的T细胞工程策略和组合方法。目前，CAR T细胞主要使用γ逆转录病毒和慢病毒载体制造，因为它们的转导效率较高。然而，人们对其安全性、按照现行良好生产规范 (cGMP) 生产的高成本、监管障碍和有限的货运能力等方面存在担忧，这些都限制了工程 T 细胞疗法的更广泛使用。为了克服这些限制，研究人员探索了非病毒方法，例如膜透化和载体介导的方法，作为下一代 T 细胞工程的更通用和可持续的替代方案。非病毒递送方法可以设计用于运输多种分子，包括 RNA，从而可以更受控和安全地调节 T 细胞表型和功能。在这篇综述中，我们概述了过继性 T 细胞疗法中的非病毒 RNA 传递。我们首先定义了不同类型的 RNA 疗法，重点介绍了其治疗用途制造方面的最新进展。然后我们讨论在 T 细胞中实现有效 RNA 递送所面临的挑战。接下来，我们概述了将 RNA 递送至 T 细胞的当前和新兴技术。最后，我们讨论正在进行的涉及 RNA 修饰 T 细胞的临床前和临床研究。