oncolytic virotherapy

溶瘤病毒疗法
  • 文章类型: Case Reports
    炎性肌纤维母细胞瘤(IMT)是一种罕见的病理实体,最早于1939年描述。这种病变最常见于肺部,但是涉及其他系统的案件,例如称为颅内IMT(IIMT)的中枢神经系统,也有报道。由于缺乏特征性的影像学变化,目前的诊断依赖于病理结果。手术切除是一种有效的治疗方法,虽然这种疾病是侵入性的,可能会复发。以前的文献报道了IMT组织中高水平的程序性死亡1(PD-1)表达,表明免疫疗法可能对这种情况有效。在这个案例报告中,我们介绍了一名中年男性,他在IIMT切除手术后接受了PD-1抑制剂和溶瘤腺病毒(Ad-TD-nsIL12)治疗.这种成功的方法为IIMT的治疗提供了新的方向。
    Inflammatory myofibroblastic tumor (IMT) is a rare pathological entity first described in 1939. This lesion is most commonly found in the lungs, but cases involving other systems, such as the central nervous system known as intracranial IMT (IIMT), have also been reported. Diagnosis currently relies on pathological results due to the lack of characteristic imaging changes. Surgical resection is an effective treatment, though the disease is invasive and may recur. Previous literature has reported a high level of programmed death 1 (PD-1) expression in IMT tissues, suggesting that immunotherapy may be effective for this condition. In this case report, we present a middle-aged male who received PD-1 inhibitor and oncolytic adenovirus (Ad-TD-nsIL12) treatment after IIMT resection surgery. This successful approach provides a new direction for the treatment of IIMT.
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  • 文章类型: Journal Article
    呼肠孤病毒(Reo)在特异性杀死肿瘤细胞方面显示出有希望的潜力,并为卵巢癌(OC)治疗提供了新的可能性。然而,OC患者腹水中的中和抗体极大地限制了Reo的进一步应用。在这项研究中,我们使用阳离子脂质体(Lipo)来递送Reo,显着增强其进入OC细胞的能力及其在腹水条件下杀死这些细胞的有效性。用MβCD抑制剂预处理显著降低Reo介导的肿瘤细胞死亡,表明Lipo主要通过小窝蛋白介导的内吞作用使Reo的细胞摄取成为可能。我们的结果表明,Lipo有效地促进Reo进入细胞质并触发细胞凋亡。上述发现为克服中和抗体在Reo临床应用中的障碍提供了新的策略。
    Reovirus (Reo) has shown promising potential in specifically killing tumor cells, and offering new possibilities for ovarian cancer (OC) treatment. However, neutralizing antibodies in the ascites from OC patients greatly limit the further application of Reo. In this study, we employed cationic liposomes (Lipo) to deliver Reo, significantly enhancing its ability to enter OC cells and its effectiveness in killing these cells under ascitic conditions. Pre-treatment with the MβCD inhibitor notably decreased Reo-mediated tumor cell death, indicating that Lipo primarily enables Reo\'s cellular uptake through caveolin-mediated endocytosis. Our results demonstrate that Lipo effectively facilitates the entry of Reo into the cytoplasm and triggers cell apoptosis. The above findings provide a new strategy to overcome the obstacle of neutralizing antibodies in the clinical application of Reo.
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  • 文章类型: Journal Article
    溶瘤病毒疗法有望为癌症提供新的治疗策略。柏油凝集素(AVL)是一种Ca2依赖性凝集素受体,含有C型凝集素的保守结构域和疏水性N末端区域,能与鸟巢糖蛋白和D-半乳糖结合。我们先前的研究表明,携带AVL基因的溶瘤痘苗病毒(oncoVV)在体内外具有显着的复制和抗肿瘤作用。在这项研究中,我们发现oncoVV-AVL可能重新编程肝癌细胞的代谢以促进ROS,和升高的ROS随后促进病毒复制并诱导细胞凋亡。本研究将为肿瘤VV-AVL在肝癌中的应用提供新的理论依据。
    Oncolytic virotherapy is expected to provide a new treatment strategy for cancer. Aphrocallistes vastus lectin (AVL) is a Ca2+-dependent lectin receptor containing the conserved domain of C-type lectin and the hydrophobic N-terminal region, which can bind to the bird\'s nest glycoprotein and D-galactose. Our previous studies suggested that the oncolytic vaccinia virus (oncoVV) armed with the AVL gene exerted remarkable replication and antitumor effects in vitro and in vivo. In this study, we found that oncoVV-AVL may reprogram the metabolism of hepatocellular carcinoma cells to promote ROS, and elevated ROS subsequently promoted viral replication and induced apoptosis. This study will provide a new theoretical basis for the application of oncoVV-AVL in liver cancer.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    除了化疗,溶瘤病毒是治疗急性髓细胞性白血病(AML)的有效方法。像其他溶瘤病毒一样,当静脉内施用时,呼肠孤病毒的抗肿瘤功效由于中和抗体的存在而降低。在这项研究中,我们评估了外泌体在人脐带间充质干细胞(UC-MSCs)向AML细胞递送呼肠孤病毒的作用.我们证明负载呼肠孤病毒的UC-MSCs可以在没有细胞接触的情况下将呼肠孤病毒递送到肿瘤细胞。我们进一步证明了外泌体抑制剂,GW4869抑制外来体的释放以及抑制呼肠孤病毒从UC-MSC向肿瘤细胞的转移。机械上,我们发现,呼肠孤病毒感染的UC-MSCs(MSCREO-EXOs)来源的外泌体具有肿瘤溶解作用,主要通过网格蛋白介导的内吞作用(CME)和巨胞作用将呼肠孤病毒传播至肿瘤细胞.此外,我们证明了使用MSC衍生的外泌体(MSC-EXO)作为呼肠孤病毒载体对AML细胞发挥抗肿瘤作用的可行性。总的来说,我们的数据表明,UC-MSCs通过外泌体释放将呼肠孤病毒转移至AML细胞,并促使进一步研究MSC-EXO作为治疗AML的潜在呼肠孤病毒载体.
    In addition to chemotherapy, oncolytic viruses are an efficient treatment for acute myeloid leukemia (AML). Like other oncolytic viruses, the anti-tumor efficacy of reovirus when administered intravenously is reduced due to the presence of neutralizing antibodies. In this study, we evaluated the role of exosomes in human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to deliver reovirus to AML cells. We show that UC-MSCs loaded with reovirus can deliver reovirus to tumor cells without cellular contact. We further demonstrate that the exosome inhibitor, GW4869, inhibits the release of exosomes as well as inhibited the transfer of reovirus from UC-MSCs to tumor cells. Mechanistically, we show that exosomes derived from reovirus-infected UC-MSCs (MSCREO-EXOs) have a tumor lysis effect and transmit reovirus to tumor cells mainly through clathrin-mediated endocytosis (CME) and macropinocytosis. In addition, we demonstrate the feasibility of using MSC-derived exosomes (MSC-EXOs) as a reovirus carrier to exert an anti-tumor effect on AML cells. Collectively, our data indicate that UC-MSCs transfer reovirus to AML cells via exosome release and prompt further study of MSC-EXOs as a potential reovirus carrier to treat AML.
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  • 文章类型: Journal Article
    肝细胞癌是一种难治性肿瘤,预后差,死亡率高。目前正在研究许多溶瘤病毒用于治疗肝细胞癌。根据以前的研究,我们构建了携带GM-CSF的辛德毕斯病毒,命名为SINV-GM-CSF,其在病毒载体的nsp1蛋白的氨基酸285处含有突变(G到S)。在细胞水平和体内验证了这种突变载体用于肝癌治疗的潜力,分别,并描述了治疗后肿瘤微环境的变化。结果表明,辛德毕斯病毒能有效感染肝癌细胞系并诱导细胞死亡。此外,GM-CSF的加入增强了辛德毕斯病毒的肿瘤杀伤作用,并增加了治疗期间肿瘤内微环境中免疫细胞的数量.特别是,在肝细胞癌的小鼠肿瘤模型中,SINV-GM-CSF能够通过调节M1型巨噬细胞(其具有肿瘤抗性能力)的升高和M2型巨噬细胞(其具有肿瘤促进能力)的减少而有效地杀死肿瘤。总的来说,SINV-GM-CSF是一种有吸引力的载体平台,具有作为安全有效的溶瘤病毒的临床潜力。
    Hepatocellular carcinoma is a refractory tumor with poor prognosis and high mortality. Many oncolytic viruses are currently being investigated for the treatment of hepatocellular carcinoma. Based on previous studies, we constructed a recombinant GM-CSF-carrying Sindbis virus, named SINV-GM-CSF, which contains a mutation (G to S) at amino acid 285 in the nsp1 protein of the viral vector. The potential of this mutated vector for liver cancer therapy was verified at the cellular level and in vivo, respectively, and the changes in the tumor microenvironment after treatment were also described. The results showed that the Sindbis virus could effectively infect hepatocellular carcinoma cell lines and induce cell death. Furthermore, the addition of GM-CSF enhanced the tumor-killing effect of the Sindbis virus and increased the number of immune cells in the intra-tumor microenvironment during the treatment. In particular, SINV-GM-CSF was able to efficiently kill tumors in a mouse tumor model of hepatocellular carcinoma by regulating the elevation of M1-type macrophages (which have a tumor-resistant ability) and the decrease in M2-type macrophages (which have a tumor-promoting capacity). Overall, SINV-GM-CSF is an attractive vector platform with clinical potential for use as a safe and effective oncolytic virus.
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  • 文章类型: Journal Article
    根据世界卫生组织的数据,癌症仍然是致命疾病的最前沿。全球观察到癌症发病率和死亡率呈上升趋势,强调应继续努力开发检测和治疗方法。诊断路径通常从学习患者的病史开始;随后是基本的血液检查和成像测试,以指示癌症可能位于何处,以安排穿刺活检。迅速开始诊断至关重要,因为延迟的癌症检测需要更高的治疗和住院成本。因此,需要新的癌症检测方法,如液体活检,弹性成像,合成生物传感器,荧光成像,和反射共聚焦显微镜。常规治疗方法,虽然在临床实践中仍然很常见,存在许多局限性,并且不能令人满意。如今,临床研究的动态发展和更精确和有效的方法的发展,如溶瘤病毒疗法,基于外泌体的治疗,纳米技术,树突状细胞,嵌合抗原受体,免疫检查点抑制剂,基于天然产品的治疗,肿瘤治疗领域,和光动力疗法。本文比较了有关常规和现代癌症检测和治疗方法的可用数据,以促进对这一迅速发展的领域及其未来方向的理解。事实证明,现代方法并非没有缺点;仍然需要开发新的检测策略和治疗方法来提高灵敏度,特异性,安全,和功效。然而,已经采取了适当的路线,食品和药物管理局批准了一些现代方法。
    In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization. Thus, there is a need for novel cancer detection methods such as liquid biopsy, elastography, synthetic biosensors, fluorescence imaging, and reflectance confocal microscopy. Conventional therapeutic methods, although still common in clinical practice, pose many limitations and are unsatisfactory. Nowadays, there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy, exosome-based therapy, nanotechnology, dendritic cells, chimeric antigen receptors, immune checkpoint inhibitors, natural product-based therapy, tumor-treating fields, and photodynamic therapy. The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions. As evidenced, modern methods are not without drawbacks; there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity, specificity, safety, and efficacy. Nevertheless, an appropriate route has been taken, as confirmed by the approval of some modern methods by the Food and Drug Administration.
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  • 文章类型: Journal Article
    最近的研究表明,溶瘤病毒与CAR-T细胞联合治疗已显示出优异的抗肿瘤效果,代表一种有希望的方法。尽管如此,肿瘤内注射的局部给药方法对治疗难以触及的转移性肿瘤或远端肿瘤提出了挑战.为了解决这个障碍,我们使用HSV-1感染的CAR-T细胞,将HSV全身递送到实体瘤中。在用HSV加载CAR-T细胞三天后,其生物学功能保持完整。在免疫受损和免疫活性GBM原位小鼠模型中,B7-H3CAR-T细胞有效地将HSV递送至肿瘤病变,导致T细胞浸润增强,并显着延长小鼠的生存期。我们还采用了双侧皮下肿瘤模型,观察到接受肿瘤内病毒注射的组在注射侧肿瘤体积显着减少,而接受静脉输注携带HSV的CAR-T细胞的组显示两侧肿瘤生长受到抑制。因此,CAR-THSV细胞在HSV向远处肿瘤的全身递送中提供显著优势。总之,我们的发现强调了CAR-T细胞作为HSV携带者的潜力,针对远处肿瘤的溶瘤病毒疗法具有显著优势。
    Recent studies have indicated that combining oncolytic viruses with CAR-T cells in therapy has shown superior anti-tumor effects, representing a promising approach. Nonetheless, the localized delivery method of intratumoral injection poses challenges for treating metastatic tumors or distal tumors that are difficult to reach. To address this obstacle, we employed HSV-1-infected CAR-T cells, which systemically delivery HSV into solid tumors. The biological function of CAR-T cells remained intact after loading them with HSV for a period of three days. In both immunocompromised and immunocompetent GBM orthotopic mouse models, B7-H3 CAR-T cells effectively delivered HSV to tumor lesions, resulting in enhanced T-cell infiltration and significantly prolonged survival in mice. We also employed a bilateral subcutaneous tumor model and observed that the group receiving intratumoral virus injection exhibited a significant reduction in tumor volume on the injected side, while the group receiving intravenous infusion of CAR-T cells carrying HSV displayed suppressed tumor growth on both sides. Hence, CAR-THSV cells offer notable advantages in the systemic delivery of HSV to distant tumors. In conclusion, our findings emphasize the potential of CAR-T cells as carriers for HSV, presenting significant advantages for oncolytic virotherapy targeting distant tumors.
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  • 文章类型: Journal Article
    溶瘤腺病毒(OAs)的治疗功效依赖于有效的病毒转导和复制。然而,柯萨奇腺病毒受体在许多肿瘤中的有限表达,随着细胞内的抗病毒信号,对OA感染和溶瘤形成重大障碍。这里,我们介绍了声敏剂武装的OAs(saOAs),它通过声动力疗法增强的病毒复制来增强溶瘤病毒疗法的抗肿瘤功效。saOAs不仅可以通过转铁蛋白受体介导的内吞作用有效感染肿瘤细胞,而且在超声照射下表现出增强的病毒复制和肿瘤溶瘤作用。我们发现,装载在病毒上的超声增敏剂诱导了肿瘤细胞内ROS的产生,触发JNK介导的自噬,最终导致病毒复制增强。在恶性黑色素瘤的小鼠模型中,SAOAs和声动力疗法的结合引发了强大的抗肿瘤免疫反应,导致显著抑制黑素瘤生长并改善宿主存活。这项工作强调了声动力疗法在增强OAs有效性方面的潜力,并为充分利用溶瘤病毒疗法的抗肿瘤功效提供了一个有希望的平台。
    The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells via transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.
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  • 文章类型: Journal Article
    新城疫病毒(NDV)是一种禽类病原体,具有未分段的负链RNA基因组,属于副粘病毒科。虽然主要在鸟类中致病,NDV对人类健康没有威胁,使其成为各种生物医学应用的安全候选物。广泛的研究强调了NDV作为疫苗开发和基因治疗载体的潜力,由于其转录模块化,低重组率,复制过程中缺乏DNA阶段。此外,NDV表现出溶瘤能力,有效引发抗肿瘤免疫反应,从而将其定位为癌症治疗的有前途的治疗剂。本文综合评述了新城疫病毒的生物学特性,阐明了其溶瘤特性的分子机制,并讨论了其在疫苗载体开发和肿瘤治疗领域的应用。
    Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome that belongs to the Paramyxoviridae family. While primarily pathogenic in birds, NDV presents no threat to human health, rendering it a safe candidate for various biomedical applications. Extensive research has highlighted the potential of NDV as a vector for vaccine development and gene therapy, owing to its transcriptional modularity, low recombination rate, and lack of a DNA phase during replication. Furthermore, NDV exhibits oncolytic capabilities, efficiently eliciting antitumor immune responses, thereby positioning it as a promising therapeutic agent for cancer treatment. This article comprehensively reviews the biological characteristics of NDV, elucidates the molecular mechanisms underlying its oncolytic properties, and discusses its applications in the fields of vaccine vector development and tumor therapy.
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