免疫治疗在急性淋巴细胞白血病中的研究进展

Advances in Immunotherapy of Acute Lymphoblastic Leukemia(ALL)

急性淋巴细胞白血病(ALL)是一种主要影响儿童和成人的血液恶性肿瘤,源于淋巴样前体细胞的恶性增殖,侵入骨髓并可扩散到髓外部位。虽然近几十年儿童ALL患者的预后得到显著改善,但儿童ALL中的某些亚组预后很差,特别是复发和难治亚组,且在这些预后不良亚组中进一步增加常规化疗强度会带来显著的不良反应。此外,使用了多种细胞毒性药物联合治疗会导致在治愈患儿中出现多种长期并发症,包括多器官功能障碍、继发癌症、精神恶化以及社会和心理问题等。迄今为止,成人ALL患者的存活率仍然较差,复发率高且治愈率不令人满意。因此,需要探索更有效和更安全的治疗方法来改善ALL患者的治疗效果。在过去十年中,免疫疗法和分子疗法的靶向治疗取得了重大进展。美国FDA已批准的基于抗体的治疗(Blinatumomab和Inotuzumab ozogamicin)和基于T细胞的治疗(Tisagenlecleucel)显著提高了复发/难治性B-ALL患者的反应率和预后。将这些免疫疗法纳入ALL治疗中,有望降低常规化疗的强度,减少相关毒性,进一步提高患者的生存率和生活质量。因此,本综述讨论了新的治疗选择,包括双特异性抗体、抗体-药物偶联物、基于嵌合抗原受体(CAR)的疗法,旨在为ALL的治疗提供新的思路和方向。

Acute lymphoblastic leukemia(ALL) is a blood cancer that primarily affects children and adults.ALL is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites.The prognosis for pediatric ALL patients has significantly improved over the past few decades,however,certain subgroups of pediatric ALL,particularly those with relapsed and refractory disease,still have poor outcomes.Further increasing in the intensity of conventional chemotherapy would be associated with significant adverse effects in these poor prognosis subgroups.In addition,the use of multiple cytotoxic drugs in combination therapy can lead to multiple long-term complications among cured patients,including multi-organ dysfunction,second cancers,mental deterioration,and social and psychological issues.To date,the survival rate in adults continues to be poor,with high relapse rates and unsatisfactory cure rates.Therefore,it is necessary to explore more effective and safer treatment methods to improve the treatment effect of ALL patients.Significant advance has been made in targeted therapy with immunotherapy and molecular therapeutics in the past 10 years.For immunotherapy,the approval of antibody-based therapy(Blinatumomab and Inotuzumab ozogamicin) and T cellbased therapy(Tisagenlecleucel) by the US FDA has significantly improved the response rate and outcomes in patients with relapsed/refractory B-ALL.Incorporating effective immunotherapy into ALL therapy would enable reduce the intensity of conventional chemotherapy,reduce associated toxicity,and further improve the survival rate and quality of life for patients with ALL.In this review,we will discuss novel therapeutic options including bispecific antibodies,antibody-drug conjugates,chimeric antigen receptor(CAR)-based therapies,to provide new ideas and directions for the treatment of ALL patients.