oncolytic virotherapy

溶瘤病毒疗法
  • 文章类型: Journal Article
    目的:为临床医生提供黑色素瘤全身治疗的指导。
    方法:美国临床肿瘤学会召集了一个专家小组,并对文献进行了最新的系统综述。
    结果:更新的综述确定了另外21项随机试验。
    新辅助派姆单抗被推荐用于可切除的IIIB期至IV期皮肤黑色素瘤患者。对于切除皮肤黑色素瘤的患者,Nivolumab或pembrolizumab是新推荐用于IIB-C期疾病的辅助治疗方案,Nivolumab联合ipilimumab是IV期疾病的潜在选择.对于不可切除或转移性皮肤黑色素瘤患者,无论BRAF突变状态如何,nivolumab+relatlimab均被添加为潜在选择,nivolumab+ipilimumab和nivolumab比BRAF/MEK抑制剂疗法更优先.Talimogenelaherparepvec不再被推荐作为抗PD-1治疗进展的BRAF野生型疾病患者的选择。在其他疗法进展后,不再推荐含有伊匹单抗和伊匹单抗的方案用于BRAF突变疾病的患者。此完整更新纳入了2022年快速建议更新中发布的针对葡萄膜黑色素瘤的新建议。其他信息可在www上获得。asco.org/黑色素瘤指南。
    To provide guidance to clinicians regarding the use of systemic therapy for melanoma.
    American Society of Clinical Oncology convened an Expert Panel and conducted an updated systematic review of the literature.
    The updated review identified 21 additional randomized trials.
    Neoadjuvant pembrolizumab was newly recommended for patients with resectable stage IIIB to IV cutaneous melanoma. For patients with resected cutaneous melanoma, adjuvant nivolumab or pembrolizumab was newly recommended for stage IIB-C disease and adjuvant nivolumab plus ipilimumab was added as a potential option for stage IV disease. For patients with unresectable or metastatic cutaneous melanoma, nivolumab plus relatlimab was added as a potential option regardless of BRAF mutation status and nivolumab plus ipilimumab followed by nivolumab was preferred over BRAF/MEK inhibitor therapy. Talimogene laherparepvec is no longer recommended as an option for patients with BRAF wild-type disease who have progressed on anti-PD-1 therapy. Ipilimumab- and ipilimumab-containing regimens are no longer recommended for patients with BRAF-mutated disease after progression on other therapies.This full update incorporates the new recommendations for uveal melanoma published in the 2022 Rapid Recommendation Update.Additional information is available at www.asco.org/melanoma-guidelines.
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  • 文章类型: Journal Article
    溶瘤病毒疗法是许多癌症的新兴治疗选择。目前正在临床试验中评估几个病毒家族。更具体地说,在几项早期临床试验中,疫苗株麻疹病毒已成为治疗不同肿瘤类型的有希望的候选者。复制病毒,尤其是没有校对聚合酶的RNA病毒,可以通过选择具有优势基因突变的准种来快速适应变化的环境。随后,这些基因改变可能会削弱病毒治疗的安全性.在这项研究中,我们证明,在生产者或癌细胞系中病毒复制的延长期之后,疫苗株来源的麻疹病毒的准种共有序列在整个非节段负链RNA基因组中产生的突变数量非常少.有趣的是,我们检测到基因组中遗传改变的非随机分布,从3'基因组开始到5'末端的突变频率总体下降。将连续传代的病毒与生产细胞上的亲本病毒进行比较,我们发现,获得性共有突变并没有显著改变病毒复制动力学或溶细胞效能.总的来说,我们的数据证实了溶瘤麻疹病毒的基因组稳定性和优异的安全性,从而支持其作为一种有前途的病毒免疫治疗的持续发展和临床翻译。
    Oncolytic virotherapy is an emerging treatment option for numerous cancers, with several virus families currently being evaluated in clinical trials. More specifically, vaccine-strain measles virus has arisen as a promising candidate for the treatment of different tumour types in several early clinical trials. Replicating viruses, and especially RNA viruses without proofreading polymerases, can rapidly adapt to varying environments by selecting quasispecies with advantageous genetic mutations. Subsequently, these genetic alterations could potentially weaken the safety profile of virotherapy. In this study, we demonstrate that, following an extended period of virus replication in producer or cancer cell lines, the quasispecies consensus sequence of vaccine strain-derived measles virus accrues a remarkably small number of mutations throughout the nonsegmented negative-stranded RNA genome. Interestingly, we detected a nonrandom distribution of genetic alterations within the genome, with an overall decreasing frequency of mutations from the 3\' genome start to its 5\' end. Comparing the serially passaged viruses to the parental virus on producer cells, we found that the acquired consensus mutations did not drastically change viral replication kinetics or cytolytic potency. Collectively, our data corroborate the genomic stability and excellent safety profile of oncolytic measles virus, thus supporting its continued development and clinical translation as a promising viro-immunotherapeutic.
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  • 文章类型: Clinical Trial, Phase III
    Talimogene laherparepvec (T-VEC) is the first intralesional therapy for melanoma approved by the U.S. Food and Drug Administration. This oncolytic viral immunotherapy has improved outcomes for patients with locoregional recurrent melanoma and is showing promise in combination with systemic therapies. 
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    This article aims to provide oncology nurses with expert guidance on best practices in incorporating intralesional therapy for patients diagnosed with melanoma in practice. 
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    Members of the Melanoma Nursing Initiative explored issues related to administration of T-VEC in melanoma. The current literature and clinical experiences were reviewed. 
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    The author offers a care step pathway (CSP) and commentary detailing best practices in infection control, drug storage, pharmacy interface, patient flow, space/staff allocation, patient education, and adverse event management with T-VEC. The CSP will help nurses improve patient outcomes and streamline the workflow with this novel therapeutic approach.
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