研究动态
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中性粒细胞介导的溶瘤菌肿瘤靶向递送系统与ICB相结合用于黑色素瘤肺转移治疗。

Neutrophil-Mediated Tumor-Targeting Delivery System of Oncolytic Bacteria Combined with ICB for Melanoma Lung Metastasis Therapy.

发表日期:2023 Aug 10
作者: Lina Liu, Wenjie Xin, Qiang Li, Baolian Huang, Te Yin, Siqi Hua, Chen Yang, Chen Chen, Chao Han, Zichun Hua
来源: Cellular & Molecular Immunology

摘要:

溶瘤细菌是最有前景的肿瘤靶向载体。关于溶瘤细菌的治疗效果和安全性之间如何取得平衡,存在一些问题。评估这种平衡的关键指标是肿瘤定植的改善程度。衰弱沙门氏菌(VNP20009)是目前唯一在临床试验中得到评估的沙门氏菌菌株,被认为是一种潜在的肿瘤治疗细菌。制备了一种控制释放VNP的输送系统,该系统将VNP装载到中性粒细胞中,显著提高了VNP对肿瘤的靶向性,并增强了在黑色素瘤肺转移模型中的治疗效果。为了改善协同治疗效果,将PD1纳米抗体应用于该系统(NE(PD1nb))。NE(PD1nb)通过激活树突状细胞(DCs)的分化,刺激巨噬细胞类似M1的分化,并通过DCs肿瘤抗原呈递,诱导CD4+ T细胞成熟和细胞毒性CD8+ T细胞的激活。 2023年作者 © Wiley-VCH GmbH出版的Advanced Science发表了本文。
Oncolytic bacteria are the most promising tumor target vector. Questions also remain regarding finding a balance between the therapeutic efficacy and safety of oncolytic bacteria. The critical measure of how this balance is maintained is the improvement in tumor colonization. Attenuated Salmonella typhimurium (VNP20009) as the only Salmonella strain to be evaluated in a clinical trial is a potential tumor therapeutic bacterium. A delivery system with controlled release of VNP after being loaded into neutrophils, which significantly increases the tumor-targeting of VNP and enhances its therapeutic efficacy in a melanoma lung metastasis model is constructed. To improve the synergistic therapeutic effect, a PD1 nanobody is applied to this system (NE(PD1nb)). NE(PD1nb) activate dendritic cells (DCs) differentiation and stimulate the M1-like differentiation of macrophages, and induce CD4+ T-cells maturity and cytotoxic CD8+ T-cells activation through DCs tumor antigen presentation.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.