Alati Caterina, Pitea Martina, Molica Matteo, Scalise Luca, Porto Gaetana, Bilardi Erica, Lazzaro Giuseppe, Micò Maria Caterina, Pugliese Marta, Canale Filippo Antonio, Loteta Barbara, Naso Virginia, Policastro Giorgia, Utano Giovanna, Rizzuto Andrea, Marafioti Violetta, Rossi Marco, Martino Massimo
Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", 89133 Reggio Calabria, Italy.
Stem Cell Transplant Program CIC587, 89133 Reggio Calabria, Italy.
Cancers (Basel). 2025 Sep 16;17(18):3027. doi: 10.3390/cancers17183027.
CAR-T therapy has transformed the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), particularly in pediatric and young adult patients. Many studies report one-year overall survival rates of between 60% and 80% following therapy. Event-free survival rates at one year are around 50-70%, with 40-50% of patients in remission after two years. Despite these impressive results, disease relapse remains a problem. Future CAR-T cell platforms should target multiple antigens, and the optimal design of such constructs must be determined. Modern trials should explore the role of CAR-T cell therapy as a consolidation treatment for patients with high-risk ALL, including those with persistent minimal residual disease at the end of induction/consolidation therapy, an IKZF1-positive gene expression profile, or a TP53 mutation or Ph-like gene expression profile. Improving the efficiency of gene-editing methods could lead to higher success rates in creating CAR-T cells, as well as reducing manufacturing time and costs. Producing universal CAR-T cells from healthy donors could significantly reduce production time and costs. These issues underscore the dynamic and evolving nature of B-ALL research. Ongoing studies and clinical trials are addressing many of these challenges in order to improve outcomes for B-ALL patients and expand the applications of CAR-T cell therapy.
嵌合抗原受体T细胞（CAR-T）疗法已经改变了复发或难治性B细胞急性淋巴细胞白血病（B-ALL）的治疗方式，尤其是在儿科和年轻成年患者中。许多研究报告称，治疗后一年的总生存率在60%至80%之间。一年的无事件生存率约为50%-70%，两年后40%-50%的患者处于缓解状态。尽管取得了这些令人瞩目的结果，但疾病复发仍然是一个问题。未来的CAR-T细胞平台应靶向多种抗原，并且必须确定此类构建体的最佳设计。现代试验应探索CAR-T细胞疗法作为高危ALL患者巩固治疗的作用，包括那些在诱导/巩固治疗结束时仍有持续性微小残留病、IKZF1阳性基因表达谱、TP53突变或Ph样基因表达谱的患者。提高基因编辑方法的效率可能会提高创建CAR-T细胞的成功率，同时减少生产时间和成本。从健康供体中生产通用CAR-T细胞可以显著减少生产时间和成本。这些问题凸显了B-ALL研究的动态性和不断发展的性质。正在进行的研究和临床试验正在应对许多这些挑战以便改善B-ALL患者的治疗结果并扩大CAR-T细胞疗法的应用。
