嵌合抗原受体治疗血液系统恶性肿瘤的现状

Current status of chimeric antigen receptor therapy for
haematological malignancies


The field of adoptive cell transfer includes chimeric antigen receptor (CAR) engineered T cells, constructs that emerged from basic research into principles of immunology and have transformed into clinically effective therapies for haematological malignancies. T cells engineered to express these artificial
receptors hold great promise, but also carry significant risk. While permanent genetic modification of mature T cells appears safe, modulating their in vivo function is difficult, partly because the robust response can trigger other arms of the immune system. Suicide systems and toxicity management with cytokine blockade or signal transduction modulators have emerged as a new frontier in this field, a far cry from early problems getting CAR T cells to work at all. Currently, clinical trials in patients with relapsed or refractory B cell malignancies treated with CD19-specific CAR T cells have induced durable remissions in adults and children. Results from these trials indicate that more work needs to be done to understand biomarkers of efficacy, the role of T cell persistence and how to integrate this care into standard practice. Cell therapy will not be a ‘one size fits all’ class of medicine, and here we will discuss the development of this therapy and important questions for its future.

嵌合抗原受体治疗血液系统恶性肿瘤的现状

过继细胞转移领域包括嵌合抗原受体（CAR）改造的T细胞，构建了从基础研究到免疫学原理，并转化为治疗血液系统恶性肿瘤的临床有效治疗方案。T细胞经过修饰表达这些人工受体具有很大的前景，但是仍然有一些风险。虽然永久基因修饰成熟T细胞似乎是安全的，但是调节它们在体内的功能是困难的，部分是因为它强大的反应可以触发免疫系统的其他部分。自杀系统和细胞因子阻断剂或信号转导调节剂的毒性管理已经成为一个新的前沿领域，一个很早就存在，使CAR-T细胞治疗成熟的关键。目前，患有复发难治性B淋巴细胞白血病的患者使用CD19特异性CAR-T细胞治疗已经在儿童和成人身上有了持久的缓解。从这些实验的结果，我们需要更多的工作来了解生物标记物的疗效，T细胞持久性的作用和如何将这些整合到标准的治疗中。细胞治疗不会是一个“一刀切”的药物，在这里我们将为它的未来讨论这个治疗的发展和一些重要的问题。