Dourthe Marie-Émilie, Yakouben Karima, Chaillou Delphine, Lesprit Emmanuelle, Dalle Jean-Hugues, Baruchel André
Service d'Hématologie Pédiatrique, Hôpital Universitaire Robert Debré (APHP), 75019 Paris, France; Université Paris Diderot, 75010 Paris, France.
Service d'Hématologie Pédiatrique, Hôpital Universitaire Robert Debré (APHP), 75019 Paris, France.
Bull Cancer. 2018 Dec;105 Suppl 2:S147-S157. doi: 10.1016/S0007-4551(19)30045-1.
Acute lymphoblastic leukemia (ALL) is the first cause of cancer in children. Five-year overall survival is greater than 90% but leukemia remains a major cause of death from cancer in children. A new class of immunotherapy based on a chimeric antigen receptor "CAR" targeting the CD19 on the B leukemic cells and that is transduced in an autologous or allogenic T lymphocyte will allow to transform the prognosis of refractory or relapsed B-ALL. Overall response rates range from 60 to 90% in phase I-II studies in patients with second relapse or more or with refractory disease. Persistent remissions and even cures have been observed. These very good results could lead to use this treatment in first line for patients with very high-risk disease. However, CAR-T cells production, costs and adverse events management represent major issues for the future of this therapeutic. The occurrence of CD19 negative relapses has led to develop bispecific CAR-T cells. Allogeneic CAR would permit to obtain a "CAR garage" off the shelf available from the diagnosis. Perspectives for CAR-T cells are immense but will involve technological progresses around the CAR conception and production, leading to further improve results in leukemias (ALL but also AML) and lymphomas and hopefully to the emergence of efficacy in childhood solid tumors. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.
急性淋巴细胞白血病(ALL)是儿童癌症的首要病因。五年总生存率超过90%,但白血病仍是儿童癌症死亡的主要原因。一类基于嵌合抗原受体“CAR”的新型免疫疗法,靶向B白血病细胞上的CD19,并在自体或异体T淋巴细胞中进行转导,将改变难治性或复发性B-ALL的预后。在针对第二次或更多次复发或难治性疾病患者的I-II期研究中,总体缓解率为60%至90%。已观察到持续缓解甚至治愈的情况。这些非常好的结果可能会导致将这种治疗用于极高风险疾病患者的一线治疗。然而,CAR-T细胞的生产、成本和不良事件管理是这种治疗未来的主要问题。CD19阴性复发的出现促使双特异性CAR-T细胞的研发。异体CAR将允许从诊断时就获得现成的“CAR库”。CAR-T细胞的前景广阔,但将涉及围绕CAR概念和生产的技术进步,从而进一步改善白血病(ALL以及AML)和淋巴瘤的治疗效果,并有望在儿童实体瘤中产生疗效。本文是在吉利德合作伙伴Kite和新基的机构支持下完成的增刊《CAR-T细胞:一场治疗革命?》的一部分。