肿瘤细胞裂解物修饰mRNA配方的高效肿瘤免疫基因治疗

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-06-02 DOI:10.1016/j.biomaterials.2025.123466

Jieping Wu , Xizi Fu , Xiaohua Chen , Ming Shuai , Mohan Liu , Jingmei Li , Yan Gao , Jin Zhang , Yi Zhun Zhu , Na Zhou , Ke Men , Xingmei Duan

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引用次数: 0

摘要

基于mrna的基因治疗在肿瘤治疗中具有重要作用。研究高效传递的mrna传递系统已成为人们关注的焦点，但对传递载体的免疫治疗能力的研究很少。肿瘤细胞裂解物是构建具有免疫刺激潜力的高级mrna传递系统的理想资源。然而，mRNA载体的有限空间和癌细胞裂解物的复杂组成阻碍了它们的联合功能。在这项研究中，我们提出了一种新的基于肿瘤细胞裂解液的mRNA递送系统，TLSV/IL- 17a（携带白细胞介素(IL)- 17a编码mRNA的肿瘤细胞裂解液载体）。TLSV在树突状细胞和肿瘤细胞中均表现出较高的mRNA递送效率。它通过特异性激活浆细胞样树突状细胞（pDCs）和自然杀伤细胞（NK）细胞，触发强大的抗癌免疫反应。通过加载IL-17A mRNA， TLSV/IL-17A有效抑制多种结肠癌模型。我们的研究结果证明了TLSV系统在肿瘤免疫治疗中的治疗潜力。

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Efficient cancer immunogenetherapy by tumor cell lysate modified mRNA formulation

mRNA-based gene therapy has an important role in cancer therapy. Intensive attention has been paid to investigate mRNA-delivery systems with high efficiency of delivery, but few studies have explored the immunotherapeutic capacity of the delivery vector. A tumor cell lysate represents an ideal resource for constructing advanced mRNA-delivery systems with immunostimulatory potential. However, the limited room of mRNA vectors and the complex composition of the cancer cell lysate are obstacles to their combined function. In this study, we present a novel tumor cell lysate-based mRNA delivery system, TLSV/IL-17A (tumor cell lysate vehicles carrying interleukin (IL)-17A-coded mRNA). TLSV demonstrates high mRNA delivery efficiency in both dendritic cells (DCs) and tumor cells. It triggers a robust anti-cancer immune response by specifically activating plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells. By loading IL-17A mRNA, the TLSV/IL-17A effectively inhibits multiple colon cancer models. Our results demonstrate the therapeutic potential of TLSV system in tumor immunogenetherapy.

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.