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老年急性髓系白血病患者的生物治疗

英文原题:Biological therapy in elderly patients with acute myeloid leukemia.

PubMed 2023/02/14(内容时间) Expert Opin Biol Ther Q2 · IF 4(JCR 2025)

研究概要

该治疗手段组合将成为多模式、个体化联合方案的基础,在精准医学理念下,将使老年 AML 患者极大获益。

中文摘要

引言:靶向分子和免疫疗法的引入正在改变急性髓系白血病(AML)的治疗格局。综述范围:本文概述可用于老年AML患者治疗的生物疗法。除靶向特定基因突变的小分子抑制剂外,抗体、肿瘤微环境调节剂和细胞疗法也正在开发,以期治愈疾病。本文报告了靶向CD33(gemtuzumab ozogamicin)或CD123(pivekimab sunirine)等表面抗原的人源化抗体和抗体药物偶联物的生物学活性、疗效和毒性;进一步探讨调节微环境的药物(如glasdegib),以及借助免疫系统对抗白血病的药物,包括CD47抗体magrolimab、PD1/PDL1抑制剂pembrolizumab和nivolumab、TIM3抑制剂sabatolimab,以及T细胞和NK细胞衔接器的作用机制和疗效。本文也考虑细胞疗法,尽管其可行性仍有大型试验尚待开展。在此背景下,本文简要介绍靶向药物的作用机制,尤其是其生物学机制。专家观点:总体而言,这些治疗手段将构成多模式、个体化联合治疗的基础;按照精准医学理念,这些方案将极大惠及老年AML患者。

展开英文摘要原文

INTRODUCTION: The introduction of target molecules and immunological therapies is changing the treatment landscape of acute myeloid leukemia (AML). AREAS COVERED: We recapitulate the biological therapies that can be employed in the treatment of elderly patients with AML. Alongside small molecules inhibitors that target specific gene mutations, antibodies, tumor microenvironment modulators, and cellular therapies are being developed for the cure of the disease. Here, we report the biological activities, the efficacy and toxicities of humanized antibodies and antibody-drug conjugates that targets surface antigens as CD33 (gemtuzumab ozogamicine) or CD123 (pivekimab sunirine). We further explore mechanisms and effectiveness of medications that modify the microenvironment, such as glasdegib, or that harness the immune system against leukemia, such as CD47 antibody magrolimab, PD1/PDL1 inhibitors pembrolizumab and nivolumab, TIM3 inhibitor sabatolimab, T-cell and NK-cell engagers. Cellular therapies are considered, even if a large trial is still pending for the feasibility of the approach. In this scenario, a brief overview of the mechanism of action of target agents is provided, particularly with respect to their biological mechanisms. EXPERT OPINION: Overall, this therapeutic armamentarium will constitute the basis for multimodal and personalized combinations that, in the idea of precision medicine, will enormously benefit elderly AML patients.

论文信息

作者
Ciotti G、Marconi G、Sperotto A、Giannini MB、Gottardi M、Martinelli G
第一作者单位
Onco Hematology, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.Italy
通讯作者单位
IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy.Italy
期刊
Expert opinion on biological therapy2023 Feb
原文标识
PubMed 36715330 · DOI 10.1080/14712598.2023.2174015