tisagenlecleucel的营销授权,第二代CD19定向的CAR-T细胞,含有4-1个BB共刺激结构域,2017年在美国和2018年在欧盟,彻底改变了儿童晚期B细胞急性淋巴细胞白血病(B-ALL)的治疗策略,青少年和年轻人(AYAs)患有复发性或难治性疾病。这种创新的治疗方法,基于“活药”,表现出非常令人印象深刻的短期反应。然而,安全概况和复杂的物流需要高度的专业知识中心和处理和处理中心之间的紧密合作。目前的研究正在探索转移到具有高风险特征和/或首次高风险复发的一线ALL的可能性。更高效的CAR-T细胞产品,仍然缺乏抵消已经描述的逃生机制。此外,定义每位患者的桥-CAR时间仍然是一个挑战,以获得最佳疾病负担,从而允许CAR-T细胞的扩增和持续存在.也很难确定谁将从输液后的进一步治疗中受益的患者,如同种异体HSCT或可进行免疫调节治疗。最后,针对T-ALL的CART细胞仅处于其开始阶段,但需要更复杂的工程过程以避免T细胞免疫缺陷或自相残杀。
The marketing authorization of tisagenlecleucel, a 2nd generation of CD19-directed CAR T-cells, containing the 4-1 BB co-stimulatory domain, in 2017 in USA and in 2018 in EU, has revolutionized the therapeutic strategy in advanced B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents and young adults (AYAs) with relapsed or refractory disease. This innovative treatment, based on a \"living drug\", has shown very impressive short-term responses. However, safety profile and complex logistics require high expertise centers and tight collaborations between addressing and treating centers. Current research is exploring the possibility to move to first line ALL with high-risk features and/or first high-risk relapse. More efficient CAR T-cells products, are still lacking to counteract the escape mechanisms already described. Moreover, to define the bridge-to-CAR time for each patient remains a challenge to obtain optimal disease burden allowing expansion and persistence of CAR T-cells. Also difficult is to identify patients who will benefit from further therapy after infusion, such as allogeneic HSCT or may be immuno-modulatory treatment. Finally, CAR T-cells directed against T-ALL are only in their beginning but require more complex engineering process to avoid T- cell immune-deficiency or fratricide.