The extraordinary success that chimeric antigen receptor (CAR) T cell therapies have shown over the years on fighting hematological malignancies is evidenced by the six FDA-approved products present on the market. CAR T treatments have forever changed the way we understand cellular immunotherapies, as current research in the topic is expanding even outside the field of cancer with very promising results. Until now, virus-based strategies have been used for CAR T cell manufacturing. However, this methodology presents relevant limitations that need to be addressed prior to wide spreading this technology to other pathologies and in order to optimize current cancer treatments. Several approaches are being explored to overcome these challenges such as virus-free alternatives that additionally offer the possibility of developing transient CAR expression or T cell modification. In this review, we aim to spotlight a pivotal juncture in the history of medicine where a significant change in perspective is occurring. We review the current progress made on viral-based CAR T therapies as well as their limitations and we discuss the future outlook of virus-free CAR T strategies to overcome current challenges and achieve affordable immunotherapies for a wide variety of pathologies, including cancer.

中文翻译：

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利用无病毒技术拓展瞬时 CAR T 疗法的视野


多年来，嵌合抗原受体 (CAR) T 细胞疗法在对抗血液恶性肿瘤方面取得了非凡的成功，市场上目前有 6 种经 FDA 批准的产品就证明了这一点。 CAR T 疗法永远改变了我们理解细胞免疫疗法的方式，因为当前该主题的研究正在扩展到癌症领域之外，并取得了非常有希望的结果。到目前为止，基于病毒的策略已用于 CAR T 细胞制造。然而，这种方法存在相关局限性，在将该技术广泛推广到其他病理学之前需要解决这些局限性，并优化当前的癌症治疗。目前正在探索多种方法来克服这些挑战，例如无病毒替代品，这些替代品还提供了开发瞬时 CAR 表达或 T 细胞修饰的可能性。在这篇综述中，我们的目的是关注医学史上正在发生重大观点转变的关键时刻。我们回顾了基于病毒的 CAR T 疗法的当前进展及其局限性，并讨论了无病毒 CAR T 策略的未来前景，以克服当前的挑战并为包括癌症在内的多种疾病实现负担得起的免疫疗法。