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首页> 外文期刊>Drug Design, Development and Therapy >Inotuzumab ozogamicin: a CD22 mAb–drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia
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Inotuzumab ozogamicin: a CD22 mAb–drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia

机译：伊诺单抗ozogamicin：一种CD22 mAb-药物偶联物，用于成人复发或难治性B细胞前体急性淋巴细胞白血病

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摘要

Despite improved rates of remission and cure in newly diagnosed adult acute lymphoblastic leukemia (ALL), the prognosis for patients with relapsed or refractory disease remains poor and the 5-year overall survival rate after relapse is under 10%. A recent paradigm shift has focused on the promise of targeted immunotherapy rather than standard chemotherapy, as ALL blast cells express a variety of antigens, and monoclonal antibodies may be developed to identify and destroy the leukemic cells. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. CD22 expression is detected on leukemic blasts in over 90% of patients with ALL. Based on promising results from preclinical studies, inotuzumab ozogamicin was tested in Phase 1/2 and Phase 3 clinical trials and it demonstrated improved complete remission rates, progression-free survival and overall survival in relapsed or refractory adult ALL compared to standard therapy. Ongoing studies are evaluating the value of inotuzumab ozogamicin when given in combination with chemotherapy as part of upfront treatment. This review discusses the drug’s biochemical properties and mechanism of action, preclinical research outcomes, clinical trial results, adverse events and toxicities, drug approval and ongoing investigations.
机译：尽管新诊断的成人急性淋巴细胞白血病（ALL）的缓解率和治愈率有所提高，但复发或难治性疾病患者的预后仍然很差，复发后的5年总生存率低于10％。最近的范式转移集中在靶向免疫疗法而不是标准化学疗法的前景上，因为ALL原始细胞表达多种抗原，单克隆抗体可能会被开发出来以鉴定和破坏白血病细胞。伊诺单抗ozogamicin是与细胞毒性抗生素calicheamicin偶联的CD22单克隆抗体。 90％以上的ALL患者在白血病母细胞中检测到CD22表达。基于临床前研究的有希望的结果，inotuzumab ozogamicin在1/2期和3期临床试验中进行了测试，与标准疗法相比，它证明了复发或难治性成人ALL的完全缓解率，无进展生存率和总体生存率得到改善。正在进行的研究正在评估将inotuzumab ozogamicin联合化疗作为前期治疗的一部分时的价值。这篇评论讨论了药物的生化特性和作用机理，临床前研究成果，临床试验结果，不良事件和毒性，药物批准以及正在进行的研究。

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