肿瘤靶向递呈载铜锰生物矿化溶瘤腺病毒用于结直肠癌免疫治疗。
Tumor-targeted delivery of copper-manganese biomineralized oncolytic adenovirus for colorectal cancer immunotherapy.
机构信息
School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; General Surgery, Cancer Center, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China.
Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China; College of Pharmacy, Hangzhou Medical College, Hangzhou 310059, China.
出版信息
Acta Biomater. 2024 Apr 15;179:243-255. doi: 10.1016/j.actbio.2024.02.044. Epub 2024 Mar 6.
Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. STATEMENT OF SIGNIFICANCE: Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.
溶瘤病毒治疗(OVT)是一种新型的抗肿瘤免疫治疗方法,特别针对肿瘤细胞进行复制。目前,溶瘤病毒主要通过瘤内注射给药。然而,对于远处转移的肿瘤,要取得良好的效果是具有挑战性的。在这项研究中,使用双金属离子铜和锰开发了一种多功能溶瘤腺病毒 OA@CuMnCs。这些金属阳离子在病毒表面形成生物矿化涂层,减少免疫清除。已知病毒会上调 PD-L1 的表达。OA@CuMnCs 中的铜离子可以降低肿瘤细胞的 PD-L1 表达,从而促进免疫细胞相关因子的释放。这个过程涉及抗原呈递和不成熟树突状细胞的结合,将其转化为成熟的树突状细胞。它将“冷”肿瘤转变为“热”肿瘤,进一步诱导免疫原性细胞死亡。虽然溶瘤病毒的复制需要氧气,但 OA@CuMnCs 中的锰离子可以与内源性过氧化氢反应。这种反应会产生氧气,增强病毒的复制能力和肿瘤裂解效应。因此,这种多功能涂层的 OA@CuMnCs 在免疫治疗效果上具有强大的放大作用,为进一步的临床 OVT 提供了巨大的潜力。
意义声明
溶瘤病毒治疗(OVT)是一种新的抗肿瘤免疫治疗方法,可以特异性地在肿瘤细胞中复制。虽然溶瘤病毒可以通过直接瘤内注射对一些非转移性肿瘤产生治疗效果,但在治疗转移性肿瘤时仍存在三个主要缺陷:免疫反应、缺氧效应和给药途径。各种研究表明,通过修饰或包裹溶瘤病毒的表面蛋白可以克服体内的免疫反应。在本文中,通过结合铜离子和锰离子的优点,制备了一种铜锰多功能涂层。该涂层具有制备方法简单、条件温和的特点,能有效增强肿瘤免疫治疗效果。