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
    CAR-T细胞疗法为延长癌症缓解提供了一种有希望的方法,特别是在血癌的情况下。然而,其在实体瘤治疗中的应用仍面临诸多局限。这篇综述文章全面概述了与CAR-T细胞治疗实体肿瘤相关的挑战和策略。专注于妇科癌症。这项研究讨论了CAR-T疗法用于实体瘤治疗的局限性,比如T细胞衰竭,基质屏障,和抗原脱落。此外,它提出了增加实体肿瘤中CAR-T功效的可能方法,包括检查点抑制剂和化疗的联合治疗,以及将CAR-T与溶瘤病毒疗法相结合的新方法。鉴于缺乏对CAR-T联合疗法治疗妇科癌症的全面研究,这篇综述旨在为实体瘤联合治疗的现状提供见解,并强调这种方法在妇科中的潜力。
    CAR-T cell therapy offers a promising way for prolonged cancer remission, specifically in the case of blood cancers. However, its application in the treatment of solid tumors still faces many limitations. This review paper provides a comprehensive overview of the challenges and strategies associated with CAR-T cell therapy for solid tumors, with a focus on gynecological cancer. This study discusses the limitations of CAR-T therapy for solid tumor treatment, such as T cell exhaustion, stromal barrier, and antigen shedding. Additionally, it addresses possible approaches to increase CAR-T efficacy in solid tumors, including combination therapies with checkpoint inhibitors and chemotherapy, as well as the novel approach of combining CAR-T with oncolytic virotherapy. Given the lack of comprehensive research on CAR-T combination therapies for treating gynecological cancers, this review aims to provide insights into the current landscape of combination therapies for solid tumors and highlight the potential of such an approach in gynecology.
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  • 文章类型: Journal Article
    溶瘤病毒(OVs)越来越被认为是癌症治疗的有效工具。有效靶向和根除致癌条件,同时保留健康细胞。它们通过在整个癌症周期中触发各种免疫反应来增强抗肿瘤免疫力。基因工程OVs迅速破坏癌组织,并通过释放可溶性抗原如危险信号和干扰素激活免疫系统。它们刺激先天和适应性免疫的能力使它们在癌症免疫疗法中特别有吸引力。最近的进步涉及将OVs与其他免疫疗法相结合,产生有希望的结果。转基因OVs,旨在增强免疫刺激并特异性靶向癌细胞,进一步改善免疫反应。这篇综述强调了OVs的内在机制,并强调了它们与其他免疫疗法的协同潜力。它还提出了优化武装OV以增强对肿瘤的免疫力的策略。
    Oncolytic viruses (OVs) are increasingly recognized as potent tools in cancer therapy, effectively targeting and eradicating oncogenic conditions while sparing healthy cells. They enhance antitumor immunity by triggering various immune responses throughout the cancer cycle. Genetically engineered OVs swiftly destroy cancerous tissues and activate the immune system by releasing soluble antigens like danger signals and interferons. Their ability to stimulate both innate and adaptive immunity makes them particularly attractive in cancer immunotherapy. Recent advancements involve combining OVs with other immune therapies, yielding promising results. Transgenic OVs, designed to enhance immunostimulation and specifically target cancer cells, further improve immune responses. This review highlights the intrinsic mechanisms of OVs and underscores their synergistic potential with other immunotherapies. It also proposes strategies for optimizing armed OVs to bolster immunity against tumors.
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  • 文章类型: Journal Article
    胶质母细胞瘤(GBM)是中枢神经系统最常见的恶性肿瘤。GBM的预后很严峻,中位总生存期为14.6个月,只有6.9%的患者在初次诊断后存活5年。尽管结果不佳,手术切除的标准疗法,放射治疗,化疗,肿瘤治疗领域基本保持不变。免疫检查点抑制剂(ICI)的引入一直是肿瘤学的范式转变,具有广泛的癌症类型的功效。尽管如此,迄今为止,新诊断和复发性GBM的ICIs调查令人失望.这种临床益处的缺乏主要归因于GBM的高度免疫抑制性质。然而,免疫疗法仍然有望治疗GBM,组合策略为潜在克服这些当前限制提供了希望。在这次审查中,我们讨论了在GBM患者中使用ICIs的临床试验的结果.之后,我们在临床前/临床证据和正在进行的临床试验的背景下,回顾了ICI组合策略以及这些组合如何克服GBM的免疫抑制微环境.
    Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system. The prognosis of GBM is grim, with a median overall survival of 14.6 months and only 6.9% of patients surviving 5 years after the initial diagnosis. Despite poor outcomes, standard therapy of surgical resection, radiotherapy, chemotherapy, and tumor-treating fields has remained largely unchanged. The introduction of immune checkpoint inhibitors (ICI) has been a paradigm shift in oncology, with efficacy across a broad spectrum of cancer types. Nonetheless, investigations of ICIs in both newly diagnosed and recurrent GBM have thus far been disappointing. This lack of clinical benefit has been largely attributed to the highly immunosuppressive nature of GBM. However, immunotherapy still holds promise for the treatment of GBM, with combinatorial strategies offering hope for potentially overcoming these current limitations. In this review, we discuss the outcomes of clinical trials employing ICIs in patients with GBM. Afterward, we review ICI combination strategies and how these combinations may overcome the immunosuppressive microenvironment of GBM in the context of preclinical/clinical evidence and ongoing clinical trials.
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  • 文章类型: Journal Article
    Ferroptosis,坏死,铁依赖控制的细胞死亡机制,以脂质过氧化物发展到致命比例为特征。恶性肿瘤,受铁的影响,促进快速发展,容易受到铁中毒的影响。基于越来越多的证据,已经观察到铁死亡可能是免疫原性的,因此可以补充免疫疗法。一种新方法包括负载氧化铁的纳米疫苗(IONVs),对肿瘤微环境(TME)的特征具有至高无上的作用,通过分子分解和靶向肿瘤细胞并诱导铁凋亡的可逆共价键提高免疫刺激能力来递送特异性抗原。除了IONVs,在肿瘤细胞中诱导铁凋亡的另一种较新的方法是通过溶瘤病毒(OVs)。一种这样的溶瘤病毒是新城疫病毒(NDV),它只能通过p53-SLC7A11-GPX4途径在癌细胞中繁殖,从而导致脂质过氧化物和细胞内活性氧水平升高,从而诱导铁细胞凋亡,从而诱导铁细胞吞噬。
    Ferroptosis, a necrotic, iron-dependent controlled cell death mechanism, is distinguished by the development of lipid peroxides to fatal proportions. Malignant tumours, influenced by iron to promote fast development, are vulnerable to ferroptosis. Based upon mounting evidence it has been observed that ferroptosis may be immunogenic and hence may complement immunotherapies. A new approach includes iron oxide-loaded nano-vaccines (IONVs), having supremacy for the traits of the tumour microenvironment (TME) to deliver specific antigens through improving the immunostimulatory capacity by molecular disintegration and reversible covalent bonds that target the tumour cells and induce ferroptosis. Apart from IONVs, another newer approach to induce ferroptosis in tumour cells is through oncolytic virus (OVs). One such oncolytic virus is the Newcastle Disease Virus (NDV), which can only multiply in cancer cells through the p53-SLC7A11-GPX4 pathway that leads to elevated levels of lipid peroxide and intracellular reactive oxygen species leading to the induction of ferroptosis that induce ferritinophagy.
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  • 文章类型: Journal Article
    最普遍的原发性恶性脑肿瘤之一是成胶质细胞瘤(GB)。每年报告每10万人约有6起事件。大多数情况下,这些肿瘤与不良预后和不良生活质量有关.GB的治疗进展甚微。近年来,一些创新药物已经过测试,用于治疗新诊断的GB病例和复发的GB病例。手术,放射治疗,和烷化剂化疗都是GB的常用治疗方法。一些潜在的替代方案包括免疫疗法,肿瘤治疗场(TTFs),和针对特定细胞受体的药物。为了提供新的多模式疗法,专注于GB中与肿瘤发生和进展有关的分子途径,新型药物,交付技术,和免疫治疗方法正在研究中。其中,溶瘤病毒(OVs)是最新的。将OVs与某些现代治疗方法结合可能对GB患者具有显著益处。这里,我们讨论了几种OV以及它们如何与其他疗法结合使用,以及GB的病毒疗法。该研究基于PRISMA指南。在PubMed上进行了系统的信息检索。在关于胶质母细胞瘤的溶瘤病毒疗法的搜索中,共发现307篇文章。这83篇文章是荟萃分析,随机对照试验,reviews,和系统的审查。从2018年到2023年,共有42篇文章。适当的研究被隔离,和重要的信息从他们中的每一个被理解,并输入到数据库中的信息,从这篇文章中使用。最常见的恶性脑肿瘤之一仍然是GB。溶瘤病毒在治疗GB和增强免疫应答中存在显著的希望和机会。在GB的治疗中充分利用OV需要仔细考虑和评估其许多应用因素。
    One of the most prevalent primary malignant brain tumors is glioblastoma (GB). About 6 incidents per 100,000 people are reported annually. Most frequently, these tumors are linked to a poor prognosis and poor quality of life. There has been little advancement in the treatment of GB. In recent years, some innovative medicines have been tested for the treatment of newly diagnosed cases of GB and recurrent cases of GB. Surgery, radiotherapy, and alkylating chemotherapy are all common treatments for GB. A few of the potential alternatives include immunotherapy, tumor-treating fields (TTFs), and medications that target specific cellular receptors. To provide new multimodal therapies that focus on the molecular pathways implicated in tumor initiation and progression in GB, novel medications, delivery technologies, and immunotherapy approaches are being researched. Of these, oncolytic viruses (OVs) are among the most recent. Coupling OVs with certain modern treatment approaches may have significant benefits for GB patients. Here, we discuss several OVs and how they work in conjunction with other therapies, as well as virotherapy for GB. The study was based on the PRISMA guidelines. Systematic retrieval of information was performed on PubMed. A total of 307 articles were found in a search on oncolytic viral therapies for glioblastoma. Out of these 83 articles were meta-analyses, randomized controlled trials, reviews, and systematic reviews. A total of 42 articles were from the years 2018 to 2023. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. One of the most prevalent malignant brain tumors is still GB. Significant promise and opportunity exist for oncolytic viruses in the treatment of GB and in boosting immune response. Making the most of OVs in the treatment of GB requires careful consideration and evaluation of a number of its application factors.
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  • 文章类型: Journal Article
    由于其对治疗的抗性,肺癌在世界范围内具有高发病率。因此,需要新的治疗方案来改善肺癌治疗的结果。这项研究旨在评估溶瘤病毒(OVs)作为一种新型癌症治疗方法的有效性。在这项研究中,回顾了PubMed和Scopus在1994年至2022年发表的158篇关于OVs在肺癌治疗中的有效性的文章。研究了八类OVs的溶瘤特性及其与治疗方案的相互作用。OVs可以作为一种有前途的免疫疗法,因为它们在不同类型的癌细胞中选择性地繁殖,导致肿瘤细胞裂解并引发有效的免疫反应。
    为了找到治疗肺癌的方法,已经进行了大量的研究。研究的方法之一是使用一种称为溶瘤病毒(OV)的病毒治疗癌症。由于肿瘤具有独特的性质,OV倾向于与它们结合并激活免疫细胞以杀死它们。本文回顾了OVs与其他常见癌症治疗方法的结合,以提高其有效性。引起更少的反应,并带来更好的结果。
    Lung cancer has a high morbidity rate worldwide due to its resistance to therapy. So new treatment options are needed to improve the outcomes of lung cancer treatment. This study aimed to evaluate the effectiveness of oncolytic viruses (OVs) as a new type of cancer treatment. In this study, 158 articles from PubMed and Scopus from 1994 to 2022 were reviewed on the effectiveness of OVs in the treatment of lung cancer. The oncolytic properties of eight categories of OVs and their interactions with treatment options were investigated. OVs can be applied as a promising immunotherapy option, as they are reproduced selectively in different types of cancer cells, cause tumor cell lysis and trigger efficient immune responses.
    A lot of research has been done to find a cure for lung cancer. Among the methods investigated is the treatment of cancer using a type of virus called an oncolytic virus (OV). Since tumors have unique properties, OVs tend to bind to them and activate immune cells to kill them. This article reviews the combination of OVs with other common cancer treatments which improves their effectiveness, causes fewer reactions and brings better results.
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  • 文章类型: Meta-Analysis
    背景:溶瘤病毒疗法治疗晚期黑色素瘤的有效性和安全性仍存在争议。有必要在临床前试验报告的基础上进行定量评价。
    方法:公开可用的数据库(PubMed,Embase,Medline,WebofScience和Cochrane图书馆。)和登记册(Clinicaltrials.gov)进行搜索,以收集溶瘤病毒疗法的治疗结果(包括1型单纯疱疹病毒(HSV),柯萨奇病毒A21(CVA21),腺病毒,痘病毒和呼肠孤病毒)用于晚期/不可切除的黑色素瘤。治疗反应的比较,不同病毒治疗的不良事件(AE)和生存分析由R软件根据来自符合条件的研究的数据进行.
    结果:最后,对34项符合条件的研究进行了分析,HSV病毒疗法的平均完全缓解率最高(CR,24.8%),HSV的平均总反应率(ORR)略高于CVA21(43.8%vs42.6%)。在比较有或没有GM-CSF/ICIs(免疫检查点抑制剂)的talimoogenelaherparepve(T-VEC)与GM-CSF/ICIs单一疗法的汇总结果中,表明病毒疗法在CR亚组中更有效(RR=1.80,95%CI[1.30;2.51],P<0.01),ORR(RR=1.17,95%CI[1.02;1.34],P<0.05),和DCR(RR=1.27,95%CI[1.15;1.40],P<0.01)。在接受T-VEC+ICIs治疗的患者中,2年总生存期(12.1±6.9个月)和无进展生存期(9.9±6.9)明显长于单独使用T-VEC治疗的患者。此外,我们发现,AEs在病毒治疗中经常发生,但在大量入选患者队列中有所下降,其中一些,如腹胀/疼痛,注射部位疼痛和瘙痒,在接受T-VEC单药治疗的患者中,发现与疾病进展呈正相关。
    结论:鉴于溶瘤病毒的相对安全性和耐受性,缺乏剂量限制依赖性毒性的报告,未来的评估分析中应增加更多接受T-VEC治疗且有或无ICIs的患者.在将其用作晚期或不可切除的黑色素瘤患者的一线治疗之前,还有很长的路要走。
    The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation on the basis of preclinical trial reports.
    Publicly available databases (PubMed, Embase, Medline, Web of Science and Cochrane Library.) and register (Clinicaltrials.gov) were searched to collect treatment outcomes of oncolytic virotherapies (including herpes simplex virus type 1 (HSV), coxsackievirus A21 (CVA21), adenovirus, poxvirus and reovirus) for advanced/unresectable melanoma. Comparisons of treatment response, adverse events (AEs) and survival analyses for different virotherapies were performed by R software based on the extracted data from eligible studies.
    Finally, thirty-four eligible studies were analysed and HSV virotherapy had the highest average complete response (CR, 24.8%) and HSV had a slightly higher average overall response rate (ORR) than CVA21 (43.8% vs 42.6%). In the pooled results of comparing talimogene laherparepve (T-VEC) with or without GM-CSF/ICIs (immune checkpoint inhibitors) to GM-CSF/ICIs monotherapy suggested virotherapy was more efficient in subgroups CR (RR = 1.80, 95% CI [1.30; 2.51], P < 0.01), ORR (RR = 1.17, 95% CI [1.02; 1.34], P < 0.05), and DCR (RR = 1.27, 95% CI [1.15; 1.40], P < 0.01). In patients treated with T-VEC+ICIs, 2-year overall survival (12.1 ± 6.9 months) and progression-free survival (9.9 ± 6.9) were significantly longer than those treated with T-VEC alone. Furthermore, we found that AEs occurred frequently in virotherapy but decreased in a large cohort of enrolled patients, some of which, such as abdominal distension/pain, injection site pain and pruritus, were found to be positively associated with disease progression in patients treated with T-VEC monotherapy.
    Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma.
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  • 文章类型: Review
    溶瘤病毒治疗正在迅速成为免疫疗法的一个有希望的子集。从理论上讲,它可以通过利用具有肿瘤细胞嗜性的病毒的复制机制来靶向肿瘤细胞,同时保留周围的健康细胞,导致直接溶瘤,并通过将免疫“冷”肿瘤转化为引发宿主免疫反应的区域。这篇综述提供了迄今为止溶瘤病毒治疗的概述,从1912年的原始概念开始。溶瘤病毒(OVs)的一般机制取决于基于病毒基因组材料的基因工程将它们选择性地整合到肿瘤细胞中,诱导溶瘤并引发宿主的先天免疫反应。此外,溶瘤病毒治疗的主要组成部分是单纯疱疹病毒,talimogenelaherparepvec是唯一FDA批准的用于治疗黑色素瘤的溶瘤病毒疗法。这篇综述探讨了其特点,优势,缺点,以及几个DNA和RNA病毒家族的治疗用途。还提供了最近和高级临床试验中使用的溶瘤病毒治疗的快照。最后,探讨了实施溶瘤病毒治疗的挑战,在分子和临床层面,突出了有希望的未来方向。特别是,缺乏基于肿瘤类型的最佳递送方法用于溶瘤病毒治疗构成了一个重大障碍,甚至在临床研究中。鞘内连续递送OVs是一个有前途的前景,可能通过调整新型连续冲洗和引流IRRAflow导管。应进一步探索和测试IRRAflow导管。
    Oncolytic viral therapy is quickly emerging as a promising subset of immunotherapy, which theoretically can target tumor cells while sparing surrounding healthy cells by harnessing the replication machinery of viruses with tropism for tumor cells, resulting in direct oncolysis, and by transforming immunologically \"cold\" tumor into areas that elicit the host\'s immune response. This review provides an overview of oncolytic viral therapy until the present day, starting with the original concept in 1912. The general mechanism of oncolytic viruses (OVs) depends on selectively integrating them into tumor cells based on genetic engineering of viral genomic material, inducing oncolysis and eliciting the host\'s innate immune response. Moreover, a major component of oncolytic viral therapy has been herpes simplex virus, with talimogene laherparepvec being the only FDA-approved oncolytic viral therapy for the treatment of melanomas. This review explores the characteristics, advantages, disadvantages, and therapeutic uses of several DNA and RNA viral families. A snapshot of the oncolytic viral treatments used in the most recent and advanced clinical trials is also provided. Lastly, the challenges of implementing oncolytic viral therapy are explored, both at a molecular and clinical level, with a highlight of promising future directions. In particular, the lack of an optimal delivery method based on tumor type for oncolytic viral therapy poses a significant obstacle, even in clinical studies. Intrathecal continuous delivery of OVs is a promising prospect, potentially by adapting the novel continuous irrigation and drainage IRRAflow catheter. Further exploration and testing of the IRRAflow catheter should be undertaken.
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  • 文章类型: Journal Article
    溶瘤病毒疗法由于能够通过全身给药引起疗效而成为人类癌症的有希望的治疗方法。肿瘤细胞通常会产生不利的免疫抑制微环境,降解病毒结构并阻碍病毒复制;然而,最近的研究表明,通过遗传修饰改变的病毒可以作为有效的溶瘤药物来对抗恶劣的肿瘤环境。具体来说,溶瘤痘苗病毒(OVV)由于其安全性而受到欢迎,全身输送的潜力,和大的基因插入能力。这篇综述重点介绍了目前关于使用工程突变病毒和基因武装的OVV逆转肿瘤微环境并增强体外和体内抗肿瘤活性的研究。并概述了正在进行的临床试验和联合疗法。此外,我们讨论了OVV作为癌症治疗的潜在利弊,探索这一领域的不同视角。
    Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration. Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication; however, recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments. Specifically, oncolytic vaccinia virus (OVV) has gained popularity owing to its safety, potential for systemic delivery, and large gene insertion capacity. This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo, and provides an overview of ongoing clinical trials and combination therapies. In addition, we discuss the potential benefits and drawbacks of OVV as a cancer therapy, and explore different perspectives in this field.
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