Genetically Reprogrammed Exosomes for Immunotherapy of Acute Myeloid Leukemia.

IF 12.1 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-01-14 DOI:10.1016/j.ymthe.2025.01.025

Lei Zhang,Guoyun Kao,Yuanteng Zhao,Zeyu Zhang,Hyo Sun Kim,Xiaojing Shi,Qinqin Cheng,Tianling Hou,Heinz-Josef Lenz,Yong Zhang

引用次数: 0

Abstract

Current treatments for acute myeloid leukemia (AML) remain challenging, characterized by poor clinical outcomes. Exosomes, cell-derived membranous vesicles, has been emerging as a new modality of therapy. Here we designed and generated genetically reprogrammed exosomes with surface displayed antibodies and immunoregulatory proteins, namely programmed immune-engaging exosomes (PRIME Exos). By simultaneously targeting T cells and AML cells expressing C-type lectin-like molecule-1 (CLL-1), PRIME Exos can elicit tumor-specific immune responses and sustain cellular immunity against AML through modulating programmed death 1 (PD-1)- and CD27-mediated immune checkpoint pathways. In preclinical models of AML, PRIME Exos are demonstrated with promising efficacy and safety for suppressing leukemia expansion. This study developed a new exosome-based approach for AML immunotherapy.

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基因重编程外泌体用于急性髓系白血病的免疫治疗。

目前治疗急性髓性白血病（AML）的方法仍然充满挑战，临床疗效不佳。外泌体是一种细胞衍生的膜囊泡，已成为一种新的治疗方式。在这里，我们设计并生成了基因重编程的外泌体，其表面显示抗体和免疫调节蛋白，即程序免疫激活外泌体（PRIME Exos）。通过同时靶向T细胞和表达C型凝集素样分子-1（CLL-1）的急性髓系白血病细胞，PRIME外泌体可通过调节程序性死亡1（PD-1）和CD27介导的免疫检查点通路，引起肿瘤特异性免疫反应并维持针对急性髓系白血病的细胞免疫。在急性髓细胞性白血病的临床前模型中，PRIME外泌体被证明在抑制白血病扩展方面具有良好的疗效和安全性。这项研究为急性髓细胞性白血病免疫疗法开发了一种基于外泌体的新方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.