抗体药物偶联物在血液肿瘤中的临床应用研究进展

doi:10.3969/j.issn.1674-8115.2024.12.015

摘要/Abstract

摘要：

抗体药物偶联物（antibody-drug conjugate，ADC）是一类由单克隆抗体和小分子细胞毒药物通过连接子偶联而成的靶向治疗药物。ADC在进入体内后，与肿瘤特异性抗原结合，形成ADC-抗原复合物；复合物通过内吞作用进入肿瘤细胞，经由内体-溶酶体途径连接子被切断，释放细胞毒药物，介导肿瘤细胞凋亡。ADC兼具单克隆抗体和细胞毒药物的双重优势，在发挥杀伤作用的同时减少了对正常细胞的损伤，因此具有更高的抗肿瘤效率。随着血液肿瘤的治疗逐渐进入靶向免疫治疗时代，ADC作为研究热点之一，展现出广阔的应用前景，但在药物研发和临床应用中也面临着许多挑战。目前已在国内上市的ADC有维布妥昔单抗（抗CD30）、奥加伊妥珠单抗（抗CD22）、维泊妥珠单抗（抗CD79B），在国外上市的还包括吉妥珠单抗（抗CD33）和朗妥昔单抗（抗CD19），它们均在临床应用中体现出良好的疗效和安全性。另外，还有针对CD123、CD19、CD20、受体酪氨酸激酶样孤儿受体1（ROR1）、CD38等血液肿瘤不同靶点的ADC正在进行相应的临床研究，而全球在研的ADC已超过100种，期待未来能取得更多突破，进一步优化血液肿瘤的治疗策略。

关键词: 抗体药物偶联物, 淋巴瘤, 白血病, 靶向治疗

Abstract:

An antibody-drug conjugate (ADC) is a targeted therapeutic drug composed of a monoclonal antibody linked to a small-molecule cytotoxic drug via a linker. Once administered, ADCs bind to tumor-specific antigens, forming ADC-antigen complexes, which are internalized through endocytosis. The linkers are then cleaved via endosomal-lysosome pathway and the cytotoxic drug is released, which induces apoptosis in the target cells. ADCs combine the advantages of monoclonal antibody drugs and cytotoxic drugs. They are able to reduce damage to normal cells while killing target cells, thus exhibiting higher anti-tumor efficiency. As the treatment of hematological malignancies gradually advances into the era of targeted immunotherapy, ADCs, as one of the hot spots, have shown broad prospects and also face many challenges in drug development and clinical application. Currently marketed ADCs in China include brentuximab vedotin (anti-CD30), inotuzumab ozogamicin (anti-CD22) and polatuzumab vedotin (anti-CD79B), while those marketed abroad include gemtuzumab ozogamicin (anti-CD33) and loncastuximab tesirine (anti-CD19), all demonstrating good efficacy and safety in clinical practice. Additionally, ADCs targeting different antigens such as CD123, CD19, CD20, receptor tyrosine kinase-like orphan receptor 1 (ROR1), and CD38 are undergoing clinical studies. Globally, there are over a hundred ADCs in development, and it is hoped that more breakthroughs will be achieved in the future to further optimize the treatment strategies for hematologic malignancies.

Key words: antibody-drug conjugate (ADC), lymphoma, leukemia, targeted therapy

中图分类号:

R733.4

唐思洁, 糜坚青. 抗体药物偶联物在血液肿瘤中的临床应用研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(12): 1607-1614.

TANG Sijie, MI Jianqing. Clinical advances in antibody-drug conjugates for hematological malignancies[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(12): 1607-1614.

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