The field of cell therapy is leading a paradigm shift in drug development. The recent convergence of several fields including immunology, genetics and synthetic biology now allows the introduction of artificial receptors and design of entire genetic circuitries to finely program the behavior of injected cells. The poster child of these next-generation living drugs are T cells expressing chimeric antigen receptors (CAR), which already demonstrated definitive evidence of therapeutic efficacy against some hematological malignancies. However, several obstacles still restrict the antitumor efficacy and impair the widespread use of CAR-T cells. Critical challenges include limited persistence and antitumor activity in vivo, antigen escape, scarcity of suitable single markers for targeting and therapy-related toxicity. Nevertheless, the intense research activity in this field has resulted in a plethora of creative solutions to address each of these limitations. In this review, we provide a comprehensive snapshot of the current strategies used to enhance therapeutic efficacy, applicability and safety of genetically engineered immune cells to treat cancer.

中文翻译：

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提高基因工程免疫细胞治疗效果、适用性和安全性的策略

细胞治疗领域正在引领药物开发的范式转变。最近包括免疫学、遗传学和合成生物学在内的几个领域的融合现在允许引入人工受体和设计整个遗传电路来精细地编程注射细胞的行为。这些下一代活体药物的典型代表是表达嵌合抗原受体 (CAR) 的 T 细胞，它已经证明了对某些血液系统恶性肿瘤的治疗功效的确切证据。然而，一些障碍仍然限制了抗肿瘤疗效并损害了 CAR-T 细胞的广泛应用。关键挑战包括体内持久性和抗肿瘤活性有限、抗原逃逸、缺乏合适的单一标记物进行靶向和治疗相关毒性。尽管如此，该领域的密集研究活动产生了大量创造性的解决方案来解决这些限制中的每一个。在这篇综述中，我们全面介绍了当前用于提高基因工程免疫细胞治疗癌症的疗效、适用性和安全性的策略。