Chimeric Antigen Receptor (CAR) T-cell therapy has become a new therapeutic reality for refractory and relapsed leukemia patients and is also emerging as a potential therapeutic option in solid tumors. Viral vector-based CAR T-cells initially drove these successful efforts; however, high costs and cumbersome manufacturing processes have limited the widespread clinical implementation of CAR T-cell therapy. Here we will discuss the state of the art of the transposon-based gene transfer and its application in CAR T immunotherapy, specifically focusing on the Sleeping Beauty (SB) transposon system, as a valid cost-effective and safe option as compared to the viral vector-based systems. A general overview of SB transposon system applications will be provided, with an update of major developments, current clinical trials achievements and future perspectives exploiting SB for CAR T-cell engineering. After the first clinical successes achieved in the context of B-cell neoplasms, we are now facing a new era and it is paramount to advance gene transfer technology to fully exploit the potential of CAR T-cells towards next-generation immunotherapy.

中文翻译：

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急性白血病中基于转座子的CAR T细胞：我们要去哪里？

嵌合抗原受体（CAR）T细胞疗法已成为难治性和复发性白血病患者的新治疗方法，并且也正在成为实体瘤的潜在治疗选择。最初，基于病毒载体的CAR T细胞推动了这些成功的努力。然而，高昂的成本和繁琐的制造过程限制了CAR T细胞疗法在临床上的广泛应用。在这里，我们将讨论基于转座子的基因转移的最新技术及其在CAR T免疫疗法中的应用，特别着重于Sleeping Beauty（SB）转座子系统，与病毒相比，它是一种有效的成本效益和安全的选择基于向量的系统。将提供SB转座子系统应用的一般概述，并更新主要进展，利用SB进行CAR T细胞工程的当前临床试验成就和未来前景。在B细胞肿瘤方面取得了第一批临床成功之后，我们现在正面临一个新时代，先进的基因转移技术对于充分利用CAR T细胞在下一代免疫疗法中的潜力至关重要。