Novel Antibody-Based Therapies For Acute Lymphoblastic Leukemia
Novel Antibody-Based Therapies For Acute Lymphoblastic Leukemia
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DOI：
10.1182/asheducation-2011.1.243
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发表时间：
2011-12-01
影响因子：
3
通讯作者：
Hoelzer, Dieter
中科院分区：
文献类型：
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作者：
Hoelzer, Dieter
急性淋巴细胞白血病 (ALL) 治疗的重大突破是针对特定转录物（例如酪氨酸激酶抑制剂 (TKI) 的 bcr-abl 融合蛋白）或单克隆抗体（mAb）的特定抗原的靶向治疗的可用性。 ALL 母细胞表达多种特异性抗原（例如 CD19、CD20、CD22、CD33 和 CD52），作为 mAb 的靶标。迄今为止，大多数数据都是抗CD20（利妥昔单抗），它与化疗联合治疗成熟B-ALL/伯基特淋巴瘤。利妥昔单抗治疗 B 前体 ALL 的研究也已完成。另一种抗原 CD19 由于在 ALL 中的表达率非常高而备受关注。它可以通过针对 CD19 和 CD3 的双特异性单克隆抗体 blinatumomab 来靶向。还提供了针对抗 CD52（阿仑单抗）、抗 CD22（依帕珠单抗）和抗 CD33（吉妥珠单抗）mAb 的小型研究或病例报告。现有数据表明，单克隆抗体治疗 ALL 是一种非常有前景的治疗方法。然而，最佳治疗方法的几个细节，例如所需的抗原表达水平、时间、时间表、剂量和疾病阶段，仍然需要确定。
A major breakthrough in the treatment of acute lymphoblastic leukemia (ALL) was the availability of targeted therapies targeting either specific transcripts, such as bcr-abl fusion protein by tyrosine kinase inhibitors (TKIs), or specific antigens by mAbs. ALL blast cells express a variety of specific antigens (eg, CD19, CD20, CD22, CD33, and CD52) that serve as targets for mAbs. To date, the most data are available for anti-CD20 (rituximab), which has been combined with chemotherapy for the treatment of mature B-ALL/Burkitt lymphoma. Studies with rituximab have also been completed in B-precursor ALL. Another antigen, CD19, is of great interest due to a very high rate of expression in ALL. It can be targeted by a bispecific mAb, blinatumomab, directed against CD19 and CD3. Smaller studies or case reports are also available for the anti-CD52 (alemtuzumab), anti-CD22 (epratuzumab), and anti-CD33 (gemtuzumab) mAbs. Available data demonstrate that mAb therapy in ALL is a highly promising treatment approach. However, several details for an optimal treatment approach, such as the required level of antigen expression, timing, schedule, dosage, and stage of disease, still need to be defined.