Radiolabeled Antibody-Drug Conjugates in the Treatment of Solid Tumors.

IF 5.9 2区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Ismaheel O Lawal, Sofiullah Abubakar, Honest Ndlovu, Aisha Ismaila, Mike M Sathekge
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Abstract

Antibody-drug conjugates (ADCs) utilize monoclonal antibodies (mAbs) that target tumor-specific antigens to deliver potent cytotoxic chemotherapy payloads to the tumor, while sparing normal tissues. The chemotherapy agents employed in ADCs are very potent, causing a tumoricidal effect at low drug concentrations. Several ADCs have been approved for the treatment of different solid tumors over the last decade following the superior efficacy and safety they demonstrated above standard-of-care treatment modalities in several clinical trials. Despite their efficacy, some patients do not respond to treatment with ADCs, as objective response rate typically range from 30% to 50%, and as low as 20% in some instances. Some patients who initially respond to treatment develop acquired resistance during their treatment, necessitating strategies to improve response rates and overcome treatment resistance. Radiation from radionuclides, with their ability to evoke a synergistic antitumor effect when used in combination with cytotoxic chemotherapy and induce a tumoricidal effect in tumor cells remote from the tumor they are bound to (crossfire effect), has the potential to improve the outcomes of ADC treatment. An expanding body of evidence, reporting the successful radiolabeling of established and experimental ADCs, is emerging in the literature. These studies have demonstrated improved antitumor effect of radiolabeled ADC relative to cold ADC, paving the way for further exploration, including in clinical settings.

放射标记抗体-药物偶联物在实体肿瘤治疗中的应用。
抗体-药物偶联物(adc)利用针对肿瘤特异性抗原的单克隆抗体(mab)向肿瘤提供有效的细胞毒性化疗有效载荷,同时不影响正常组织。adc中使用的化疗药物非常有效,在低药物浓度下就能产生杀瘤作用。在过去的十年中,几种adc已被批准用于治疗不同的实体肿瘤,因为它们在几项临床试验中显示出优于标准治疗模式的疗效和安全性。尽管adc有疗效,但一些患者对其治疗没有反应,因为客观反应率通常在30%至50%之间,在某些情况下低至20%。一些最初对治疗有反应的患者在治疗期间出现了获得性耐药,需要采取策略来提高反应率并克服治疗耐药。放射性核素的辐射在与细胞毒性化疗联合使用时能够引起协同抗肿瘤作用,并在远离其所结合肿瘤的肿瘤细胞中诱导杀瘤作用(交叉火力效应),具有改善ADC治疗结果的潜力。文献中出现了越来越多的证据,报告了已建立的和实验性adc的成功放射性标签。这些研究表明,放射性标记ADC的抗肿瘤效果优于冷ADC,为进一步探索铺平了道路,包括在临床环境中。
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来源期刊
Seminars in nuclear medicine
Seminars in nuclear medicine 医学-核医学
CiteScore
9.80
自引率
6.10%
发文量
86
审稿时长
14 days
期刊介绍: Seminars in Nuclear Medicine is the leading review journal in nuclear medicine. Each issue brings you expert reviews and commentary on a single topic as selected by the Editors. The journal contains extensive coverage of the field of nuclear medicine, including PET, SPECT, and other molecular imaging studies, and related imaging studies. Full-color illustrations are used throughout to highlight important findings. Seminars is included in PubMed/Medline, Thomson/ISI, and other major scientific indexes.
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