肿瘤细胞治疗研究
英文原题：Immunotherapy in B-Cell Acute Lymphoblastic Leukemia.
近年来，免疫治疗已越来越多地被纳入儿童和成人 B 细胞急性淋巴细胞白血病（B-ALL）患者的临床诊疗中，以改善结局。
近年来，免疫疗法日益纳入儿童和成人B细胞急性淋巴细胞白血病（B-ALL）的临床治疗，以改善患者结局。B-ALL免疫疗法主要包括四类：（1）非偶联单克隆抗体（mAb）；（2）抗体药物偶联物（ADC）；（3）T细胞衔接抗体；（4）CAR-T细胞。利妥昔单抗等mAb主要用于成人，而其他疗法在儿童和成人B-ALL中均显示疗效。在ADC中，奥加伊妥珠单抗（InO）单药治疗复发疾病已证实有效，因此FDA批准其用于年龄大于1岁的复发/难治性B-ALL患者。InO联合化疗用于初始治疗也正在研究。虽然成人研究结果令人鼓舞，但InO治疗后后续化疗期间感染并发症增加，阻碍了儿童、青少年及青年患者试验的推进。随着双特异性T细胞衔接器贝林妥欧单抗成功纳入成人和儿童化疗方案，T细胞衔接抗体现已成为多数新诊断及复发B-ALL患者治疗的标准组成部分。近期研究支持使用贝林妥欧单抗替代B-ALL传统治疗中的部分甚至大部分强化化疗。靶向CD19的CAR-T疗法革新了复发/难治性B-ALL治疗，但仍面临CAR-T持续性不足和抗原逃逸等挑战。为解决抗原逃逸问题，研究者正在评估靶向CD22或同时靶向CD19和CD22的新型CAR-T。总体而言，免疫疗法已成为B-ALL治疗的基石。本文回顾多种B-ALL免疫疗法的疗效和安全性数据，并讨论尚待解决的问题及未来可能方向。
In recent years, immunotherapy has been increasingly incorporated into the clinical care of both pediatric and adult patients with B-cell acute lymphoblastic leukemia (B-ALL) to improve outcomes. Four main categories of immunotherapies are used in B-ALL: (1) unconjugated monoclonal antibodies (mAbs), (2) antibody-drug conjugates (ADCs), (3) T-cell-engaging antibodies, and (4) CAR T cells. Although mAbs such as rituximab are primarily used in adults, the other modalities have demonstrated efficacy in both pediatric and adult patients with B-ALL. Among ADCs, inotuzumab ozogamicin (InO) has proven effective as monotherapy for relapsed disease, leading to FDA approval for patients aged >1 year with relapsed/refractory B-ALL. InO is also being investigated in the upfront setting in combination with chemotherapy. Although results in adults have been promising, increased rates of infectious complications in chemotherapy courses post-InO have hampered progress of trials in children, adolescents, and young adults. T-cell-engaging antibodies are now a standard component of therapy for most patients with newly diagnosed and relapsed B-ALL, following the successful integration of the bispecific T-cell-engager blinatumomab into chemotherapy regimens for both adults and children. Recent studies support the possibility of using blinatumomab to replace some or even most of the intensive chemotherapy traditionally used in B-ALL treatment. CAR T-cell therapy has revolutionized the treatment of relapsed/refractory B-ALL by targeting CD19, but challenges remain due to the loss of CAR T-cell persistence and antigen escape. Newer CAR T cells targeting CD22 or the combination of CD19 and CD22 are being studied to address the issue of antigen escape. Overall, immune-based therapies are now a mainstay of B-ALL therapy. This article reviews the efficacy and safety data of several immune-based therapies in B-ALL and discusses a number of outstanding questions and possible future directions for the use of immune-based approaches in the treatment of B-ALL.
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