Engineered bacteria for near-infrared light-inducible expression of cancer therapeutics.

IF 28.5 1区医学 Q1 ONCOLOGY

Nature cancer Pub Date : 2025-04-01 Epub Date: 2025-03-17 DOI:10.1038/s43018-025-00932-3

Longliang Qiao, Lingxue Niu, Zhihao Wang, Zhenqiang Deng, Dai Di, Xiaoding Ma, Yang Zhou, Deqiang Kong, Qilin Wang, Jianli Yin, Lingli Jin, Jing Sun, Bo Feng, Weiqiang Lu, Fengfeng Cai, Ningzi Guan, Haifeng Ye

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引用次数: 0

Abstract

Bacteria-based therapies hold great promise for cancer treatment due to their selective tumor colonization and proliferation. However, clinical application is hindered by the need for safe, precise control systems to regulate local therapeutic payload expression and release. Here we developed a near-infrared (NIR) light-mediated PadC-based photoswitch (NETMAP) system based on a chimeric phytochrome-activated diguanylyl cyclase (PadC) and a cyclic diguanylate monophosphate-dependent transcriptional activator (MrkH). The NETMAP-engineered bacteria exhibited antitumor performance in mouse tumor models with different levels of immunogenicity. Specifically, in immunogenic lymphoma tumors, NIR-induced PD-L1 and CTLA-4 nanobodies enhanced the activation of adaptive immunity. In low-immunogenic tumors-including mouse-derived colon cancer models, an orthotopic human breast cancer cell line-derived xenograft model and a colorectal cancer patient-derived xenograft model-NIR-induced azurin and cytolysin A predominantly led to tumor inhibition. Our study identifies an NIR light-mediated therapeutic platform for engineered bacteria-based therapies with customizable outputs and precise dosage control.

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用于近红外线诱导表达癌症治疗药物的工程细菌。

基于细菌的治疗因其选择性肿瘤定植和增殖而在癌症治疗中具有很大的前景。然而，由于需要安全、精确的控制系统来调节局部治疗有效载荷的表达和释放，临床应用受到阻碍。在这里，我们开发了一种近红外（NIR）光介导的基于PadC的光开关（NETMAP）系统，该系统基于嵌合光敏色素激活的二胍基环化酶（PadC）和环二胍酸单磷酸依赖的转录激活剂（MrkH）。在不同免疫原性水平的小鼠肿瘤模型中，netmap工程细菌均表现出抗肿瘤性能。具体来说，在免疫原性淋巴瘤肿瘤中，nir诱导的PD-L1和CTLA-4纳米体增强了适应性免疫的激活。在低免疫原性肿瘤（包括小鼠来源的结肠癌模型、原位人乳腺癌细胞系来源的异种移植模型和结直肠癌患者来源的异种移植模型）中，nir诱导的azurin和胞溶素a主要导致肿瘤抑制。我们的研究确定了一个近红外光介导的治疗平台，用于基于工程细菌的治疗，具有可定制的输出和精确的剂量控制。

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

Nature cancer Medicine-Oncology

CiteScore

31.10

自引率

1.80%

发文量

129

期刊介绍： Cancer is a devastating disease responsible for millions of deaths worldwide. However, many of these deaths could be prevented with improved prevention and treatment strategies. To achieve this, it is crucial to focus on accurate diagnosis, effective treatment methods, and understanding the socioeconomic factors that influence cancer rates. Nature Cancer aims to serve as a unique platform for sharing the latest advancements in cancer research across various scientific fields, encompassing life sciences, physical sciences, applied sciences, and social sciences. The journal is particularly interested in fundamental research that enhances our understanding of tumor development and progression, as well as research that translates this knowledge into clinical applications through innovative diagnostic and therapeutic approaches. Additionally, Nature Cancer welcomes clinical studies that inform cancer diagnosis, treatment, and prevention, along with contributions exploring the societal impact of cancer on a global scale. In addition to publishing original research, Nature Cancer will feature Comments, Reviews, News & Views, Features, and Correspondence that hold significant value for the diverse field of cancer research.