18年1月份溶瘤病毒相关SCI文章（二区以上）选辑
来源：溶瘤病毒之家
Web of Science显示在2018年1月1日-31日期间正式发表的溶瘤病毒SCI文章（二区以上）选辑
编辑：陈安仙，吴俊华
策划：吴俊华
顾问：魏继武
1、Solid Tumor Immunotherapy with T Cell Engager-ArmedOncolytic Viruses
出版物: Macromolecularbioscience（IF2017=3.238，二区）
DOI:10.1002/mabi.201700187
文章类型：综述与评论
文章主要内容：溶瘤病毒是一种新型的抗肿瘤药物，它具有直接杀死肿瘤细胞和刺激抗肿瘤免疫的双重作用。此外，溶瘤病毒能够被改造用于直接递送生物疗法到肿瘤上，为设计多形式抗癌策略提供独特的机会。这篇综述重点阐述了一种溶瘤病毒与其他治疗方法联合的策略：给复制型溶瘤病毒“武装”上一种以T细胞作为效应细胞的双特异性单链抗体（BiTEs，具有两个抗原结合臂,可以同时和T细胞及靶细胞结合,并激活细胞毒性T细胞杀伤病变细胞），在对抗许多血液肿瘤时表现出疗效。然而，在治疗实体瘤时给复制型溶瘤病毒“武装”上BiTEs的成功显得很有限，至少部分归因于：1.差的递送动力学和渗透到肿瘤里去的能力差；2.off-tumor 活性，导致剂量限制的毒性。给复制型溶瘤病毒“武装”上BiTEs，这样做的好处是：1）可以使得以T细胞作为效应细胞的双特异性单链抗体在肿瘤部位表达，带来了靶向性；2）降低了脱靶效应，增大了治疗窗口；3）与病毒的溶瘤效应构成协调作用。本综述总结到目前为止BiTEs-armed 溶瘤病毒的临床前的主要进展，并且探索共同靶向肿瘤细胞和非转化基质细胞的可能性。
附原文摘要：
Oncolytic viruses (OVs) are novel anticancer agents that combine directcancer cell killing with the stimulation of antitumor immunity. In addition,OVs can be engineered to deliver biological therapeutics directly to tumors,offering unique opportunities to design multimodal anticancer strategies. Here,a case for arming OVs with bispecific T cell engagers (BiTEs) is put forward.BiTEs redirect the cytotoxicity of polyclonal T cells to target cells ofchoice, and have demonstrated efficacy against a number of hematologicalcancers. However, the success of BiTEs in the treatment of solid tumors appearsmore limited, at least in part due to: (i) poor delivery kinetics and penetrationinto tumors, and (ii) on-target off-tumor activity, leading to dose-limitingtoxicities. Linking the production of BiTEs to OV replication provides anexciting means to restrict production to the tumor site, widen theirtherapeutic window, and synergize with direct oncolysis. This review summarizesprogress thus far in the preclinical development of BiTE-armed OVs, andexplores the possibility of cotargeting cancer cells and nontransformed stromalcells.
2、Toxicity profiles of immunotherapy
出版物: Pharmacology& therapeutics（IF2017=11.127，一区）
DOI: 10.1016/j.pharmthera.2017.07.005
文章类型：综述与评论
文章主要内容：免疫疗法正在改变晚期实体瘤治疗的形势，这些治疗有不同的作用机制，包括溶瘤病毒和免疫检测定抑制剂在内的肿瘤免疫治疗受到越来越多的重视，也展现出巨大的前景，其中免疫检测定抑制剂主要有CTLA-4或者PD-1/PD-L1单克隆抗体，以及CSF-1R抗体。考虑到这些药物在肿瘤治疗方面将会产生深远的影响，理解他们的性质显得十分重要。作为新的治疗方法，其副作用也是需要关注的重要主题，这篇综述重点阐述免疫治疗副作用产生的机制，已经应对的方法和策略。这篇文章的第三部分重点给大家介绍溶瘤病毒疗法安全性的总体评价、毒副作用产生的机制。
附原文摘要：
Immunotherapies are changing the landscape of advanced solid tumortreatment. These therapies have different mechanisms of action and includeoncolytic viruses, checkpoint inhibitors, such as CTLA-4 or PD1/PD-L1monoclonal antibodies, and CSF-1R antibodies. Given the growing therapeuticimpact of these agents in oncology, it is important to better understand theirproperties. Immunotherapies generate new toxicity profiles that are calledimmune-related adverse events and require specific management. This reviewfocuses on the mechanisms of action of such side effects, as well as theirdescription and their general management.
3、 Comparative Oncology Evaluation ofIntravenous Recombinant Oncolytic Vesicular Stomatitis Virus Therapy inSpontaneous Canine Cancer
出版物: MOLECULAR CANCER THERAPEUTICS（IF2017=5.764，二区）
DOI:10.1158/1535-7163.MCT-17-0432
文章类型：研究文章
文章主要内容：静脉注射治疗用于治疗扩散的或转移的癌症的临床转化是势在必得的。比较肿瘤学，在自发性癌症的动物上的新型癌症治疗评估能够被用来加速临床转化。本研究构建了一个重组的水泡性口膜炎病毒VSVIFNb-NIS，临床前小鼠研究表明单次系统性用VSVIFNb-NIS治疗，在荷瘤小鼠上可以诱导治疗缓解。然而，VSV-IFNb-NIS能否用于临床治疗依赖于临床毒性、病毒散播、药物代谢动力学和疗效在临床相关模型中的综合评估。狗自发地患上癌症和人类恶性肿瘤有相似的病因、临床进展以及治疗反应，本研究开展了一种比较肿瘤学研究，用来研究在自发性肿瘤的宠物狗身上静脉注射溶瘤VSVIFNb-NIS治疗的可行性和耐受度。用VSV-IFNb-NIS病毒单次静脉内给予具有各种恶性肿瘤的九只狗，进行治疗。两只患有高度恶性外周T细胞淋巴瘤的狗病情得到迅速但暂时的缓解，同时也出现了短暂的肝毒性。没有检测到传染性病毒的脱落。相关的药代动力学研究显示在可以测量到疾病得到缓解的狗血液中VSV病毒RNA的水平是升高的。这是第一个关于静脉给予溶瘤病毒用于治疗自发性犬癌症的研究，这个研究证明VSV-IFNb-NIS在晚期或转移性肿瘤的狗中耐受良好且安全。这个研究为临床转化提供了非常重要的信息，包括剂量和靶标等指示的选择。
附原文摘要：
Clinical translation of intravenous therapies to treat disseminated ormetastatic cancer is imperative. Comparative oncology, the evaluation of novelcancer therapies in animals with spontaneous cancer, can be utilized to informand accelerate clinical translation. Preclinical murine studies demonstratethat single-shot systemic therapy with a vesicular stomatitis virus (VSV)-IFNb-NIS,a novel recombinant oncolytic VSV, can induce curative remission intumor-bearing mice. Clinical translation of VSV-IFNb-NIS therapy is dependenton comprehensive assessment of clinical toxicities, virus shedding,pharmacokinetics, and efficacy in clinically relevant models. Dogsspontaneously develop cancer with comparable etiology, clinical progression,and response to therapy as human malignancies. A comparative oncology study wascarried out to investigate feasibility and tolerability of intravenousoncolytic VSVIFNb-NIS therapy in pet dogs with spontaneous cancer. Nine dogswith various malignancies were treated with a single intravenous dose ofVSV-IFNb-NIS. Two dogs with high-grade peripheral T-cell lymphoma had rapid buttransient remission of disseminated disease and transient hepatotoxicity thatresolved spontaneously. There was no shedding of infectious virus. Correlativepharmacokinetic studies revealed elevated levels of VSV RNA in blood in dogswith measurable disease remission. This is the first evaluation of intravenousoncolytic virus therapy for spontaneous canine cancer, demonstrating thatVSV-IFNb-NIS is well-tolerated and safe in dogs with advanced or metastaticdisease. This approach has informed clinical translation, including dose andtarget indication selection, leading to a clinical investigation of intravenousVSVIFNb- NIS therapy, and provided preliminary evidence of clinical efficacyand potential biomarkers that correlate with therapeutic response.
4、Sensitizing hepatocellular carcinoma to oncolytic virustherapy
出版物: NATURE REVIEWS GASTROENTEROLOGY &HEPATOLOGY（IF2017=13.678，一区）
DOI:10.1038/nrgastro.2017.153
文章类型：综述评论
文章主要内容：该文是对 Zhang, H. et al. TargetingVCP enhances anticancer activity of oncolytic virus M1 in hepatocellularcarcinoma. Sci. Transl Med. 9, eaam7996 (2017) 的评述。溶瘤病毒已经成为头条，主要归因于越来越多临床上成功的报告。引人注目的数据表明抗癌小分子化合物可以用作为肝细胞肝癌治疗中的强效敏化剂，以便增强系统性给予病毒的溶瘤潜力。
附原文摘要：
Oncolytic viruses have made headlines owing to increasing numbers ofreports of clinical success. Compelling data now indicate that small anticancermolecules can serve as potent sensitizers of tumour cells in hepatocellularcarcinoma to enhance the oncolytic potential of systemically applied viruses.
5、Oncolytic Virus: Regulatory Aspects from Quality Controlto Clinical Studies
出版物: CURRENT CANCERDRUG TARGETS（IF2017=2.992，二区）
DOI: 10.2174/1568009617666170222142650
文章类型：综述评论
文章主要内容：溶瘤病毒包括天然野生型病毒/减弱病毒和基因改造的病毒最近已经用于新型的癌症治疗。基因改造的溶瘤病毒作为一个独特的基因治疗产物拥有独特的能力去有条件地复制。由于溶瘤病毒已经在病人身上展示出延长生存的作用，因此病毒散发和传播到其他人，以及临床安全性和疗效应该是临床试验的主要关注点。正因为如此，大量的研究正在评估溶瘤病毒的安全性和疗效。
附原文摘要：
Oncolytic viruses, which include both naturally occurring wild-typeviruses/attenuated viruses and genetically modified viruses, have recently beendeveloped for use in innovative cancer therapies. Genetically modifiedoncolytic viruses possess the unique ability to replicate conditionally as aunique gene therapy product. Since oncolytic viruses exhibit prolongedpersistence in patients, viral shedding and transmission to third partiesshould be major concerns for clinical trials along with the clinical safety andefficacy. Accordingly, studies are now underway to establish the safety andefficacy of oncolytic viruses.
6、 Oncolytic Virotherapy and Gene TherapyStrategies for Hepatobiliary Cancers
出版物: CURRENT CANCERDRUG TARGETS（IF2017=2.992，二区）
DOI: 10.2174/1568009617666170330123841
文章类型：综述评论
文章主要内容：由于频繁的局部侵袭和转移，晚期肝癌和胆管癌是预后很差的疾病代表，针对这些癌症的有效治疗药物还没开发出来。溶瘤病毒是一种新的有前途的疗法，该疗法具有抗肿瘤的选择性，而且近期研究也展示了该疗法独有的特征。此外，临床试验结果表明该疗法大有前景。许多溶瘤病毒正在临床前模型中接受肝癌试验。头号制剂Pexa-Vec，一种重组惠氏菌株疫苗病毒，已经在临床试验中展示出治疗肝癌的安全性和有效性。对于胆管癌来说临床前研究和临床试验相对很少。在本综述里，我们介绍各种使用溶瘤病毒的方法治疗难治的肝胆癌症。
附原文摘要：
Advanced liver cancers andbiliary cancers represent diseases with dismal prognosis because of frequentlocal invasion and metastasis. Effective therapeutic agents for these cancershave not been established. Oncolytic viruses (OVs) constitute a novel class ofpromising, selective anticancer agents and recent studies have elucidated theirunique features. Moreover, clinical trials are demonstrating promising results.Numerous OVs are being tested in preclinical models of hepatocellular carcinoma(HCC). The lead agent Pexa-Vec (pexastimogene devacirepvec, JX-594), arecombinant Wyeth strain vaccinia virus, has demonstrated preliminary evidenceof safety and efficacy for HCC in clinical trials. Few other OVs have enteredclinical testing. Relatively few preclinical studies and clinical trials existfor biliary cancers. In this review, we introduce various approaches using OVsto treat the intractable hepatobiliary cancers.
7、 Clinical Trials with Oncolytic Measles Virus: Current Status and FutureProspects
出版物: CURRENT CANCER DRUG TARGETS（IF2017=2.992，二区）
DOI:10.2174/1568009617666170222125035
文章类型：综述评论
文章主要内容：减毒的Edmonston 麻疹病毒疫苗株能优先感染和裂解很多种类型的肿瘤细胞。溶瘤麻疹病毒通过基因改造来表达人类癌胚抗原或者人钠碘转运体并且现在正在临床试验用于治疗卵巢癌、多型性成胶质细胞瘤、多发性骨髓瘤、间皮瘤、头颈部肿瘤、乳腺癌以及恶性外周神经鞘瘤。本综述重点描述促进MV-Edm临床转化的基础和临床数据，并且总结目前为止溶瘤病毒平台的临床结果。此外，我们讨论最新的临床相关的MV-Edm载体发展和有创造性的未来转化策略。
附原文摘要：
AttenuatedEdmonston lineage measles virus (MV-Edm) vaccine strains can preferentiallyinfect and lyse a wide variety of cancer cells. Oncolytic MV-Edm derivativesare genetically engineered to express the human carcinoembryonic antigen(MV-CEA virus) or the human sodium iodide symporter (MV-NIS virus) and arecurrently being tested in clinical trials against ovarian cancer, glioblastomamultiforme, multiple myeloma, mesothelioma, head and neck cancer, breast cancerand malignant peripheral nerve sheath tumors. This review describes the basicand preclinical data that facilitated the clinical translation of MV-Edmstrains, and summarizes the clinical results of this oncolytic platform todate. Furthermore, we discuss the latest clinically relevant MV-Edm vectordevelopments and creative strategies for future translational steps.
8、 Oncorine, the World First Oncolytic Virus Medicine and its Update in China
出版物: CURRENT CANCERDRUG TARGETS（IF2017=2.992，二区）
DOI: 10.2174/1568009618666171129221503
文章类型：综述评论
文章主要内容：溶瘤病毒现在已经成为一种最有希望的癌症治疗策略之一。从1998年开始，在中国溶瘤病毒的概念已经激发了一波又一波为了这类研究实现临床转化的商业性研究和开发活动。世界上首个商业化的溶瘤病毒产品“安柯瑞（H101）”，从1999年开始，由上海三维生物科技有限公司开发，并且于2005年被中国国家食品药品监督管理局（CFDA）批准用于III期临床试验后，主要是联合化疗药物治疗鼻咽癌，“安柯瑞（H101）”最终于2006年8月获得CFDA批准上市。本综述主要介绍“安柯瑞（H101）”是怎样在中国成功的，并且在2006年进入市场后中国市场的反应如何。
附原文摘要：
The oncolyticviruses now hold a promise of new therapeutic strategy for cancer. Its concepthas inspired a wave of commercial research and development activities for theproducts of this category in China since 1998. The first commercializedoncolytic virus product in the world, On-corine (H101), developed by ShanghaiSunway Biotech Co., Ltd since 1999, was approved by Chinese SFDA in November,2005 for nasopharyngeal carcinoma in combination with chemotherapy after thephase III clinical trial, and finally acquired GMP certificate in August, 2006.This review introduces how Oncorine was successfully developed in China, andhow the Chinese market responded after it was launched into the market in 2006.
9、 Oncolytic Herpes Simplex Virus Vectors Fully Retargeted toTumor-Associated Antigens
出版物: CURRENT CANCERDRUG TARGETS（IF2017=2.992，二区）
DOI: 10.2174/1568009617666170206105855
文章类型：综述评论
文章主要内容：溶瘤病毒疗法是一种新型的利用病毒在肿瘤细胞里选择性复制的原理用于恶性疾病的治疗方法。由于单纯性疱疹病毒（HSV）具有广泛的细胞趋向性和比起正常细胞更倾向在肿瘤细胞里复制（突变方式）的特性，HSV已经成为一种有前途的用于溶瘤病毒疗法的制剂。然而，这些突变也倾向于限制当前进入临床研究的溶瘤HSV载体的治疗潜力。作为替代方案，病毒载体重新定位于新的感染受体，拥有在病毒进入阶段实现具有感染肿瘤特异性的潜力，排除了复制减弱方面的突变需求。在这篇文章中，作者总结了HSV进入的分子机制和近期在完全重定向HSV载体用于溶瘤病毒治疗发展的进展。HSV重靶向载体为新一代特异性溶瘤HSV的产生提供了一个吸引人的平台。
附原文摘要：
Oncolyticvirotherapy is a novel therapeutic modality for malignant diseases thatexploits selective viral replication in cancer cells. Herpes simplex virus(HSV) is a promising agent for oncolytic virotherapy due to its broad celltropism and the identification of mutations that favor its replication in tumorover normal cells. However, these attenuating mutations also tend to limit thepotency of current oncolytic HSV vectors that have entered clinical studies. Asan alternative, vector retargeting to novel entry receptors has the potentialto achieve tumor specificity at the stage of virus entry, eliminating the needfor replication-attenuating mutations. Here, we summarize the molecularmechanism of HSV entry and recent advances in the development of fullyretargeted HSV vectors for oncolytic virotherapy. Retargeted HSV vectors offeran attractive platform for the creation of a new generation of oncolytic HSVwith improved efficacy and specificity.
10、 Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System
出版物: CURRENT CANCERDRUG TARGETS（IF2017=2.992，二区）
DOI: 10.2174/1568009617666170502152352
文章类型：综述评论
文章主要内容：腺病毒是最常使用的用于基因治疗的载体之一，并且它是首个被批准用于治疗癌症的溶瘤病毒药物。作为一个溶瘤试剂，它能诱导感染的细胞裂解，而且它也能够参与免疫系统，促进抗原呈递细胞（APC）的活化和成熟。本质上，溶瘤作用联合免疫刺激性措施会为每个病人产生一个个体化原位疫苗。为了充分利用这些特征，我们应该努力去理解腺病毒是如何与免疫系统相互作用的。有哪些受体参与触发后续的信号，它们会引起哪类反应。抓住这些问题将会使我们明白怎样去操作腺病毒介导的免疫反应增强抗肿瘤疗效。在这篇综述中，作者首先强调溶瘤腺病毒是怎样与免疫系统相互作用以及如何与免疫相关的受体相互作用的，比如Toll样受体、NOD样受体和其他免疫感受器。然后作者描述这些适应性免疫系统和它的细胞之间相互作用的效应，特别是B和T淋巴细胞。最后，作者总结在研究者人员已经应用腺病毒表达细胞因子和信号调节分子来调空宿主免疫系统的基因治疗领域里最有意义的临床前和临床研究结果。
附原文摘要：
Adenovirus isone of the most commonly used vectors for gene therapy and it is the firstapproved virus-derived drug for treatment of cancer. As an oncolytic agent, itcan induce lysis of infected cells, but it can also engage the immune system,promoting activation and maturation of antigen-presenting cells (APCs). Inessence, oncolysis combined with the associated immunostimulatory actionsresult in a "personalized in situ vaccine" for each patient. In orderto take full advantage of these features, we should try to understand howadenovirus interacts with the immune system, what are the receptors involved intriggering subsequent signals and which kind of responses they elicit. Tacklingthese questions will give us further insight in how to manipulateadenovirus-mediated immune responses for enhancement of anti-tumor efficacy.
In this review,we first highlight how oncolytic adenovirus interacts with the innate immunesystem and its receptors such as Toll-like receptors, nucleotide-binding andoligomerization domain (NOD)-like receptors and other immune sensors. Then wedescribe the effect of these interactions on the adaptive immune system and itscells, especially B and T lymphocytes. Finally, we summarize the mostsignificant preclinical and clinical results in the field of gene therapy whereresearchers have engineered adenovirus to manipulate the host immune system byexpressing cytokines and signal-ingmediators.
11、 Oncolytic Viruses: The Best is Yet to Come
出版物: CURRENT CANCERDRUG TARGETS（IF2017=2.992，二区）
DOI:10.2174/1568009617666170206111609
文章类型：综述评论
文章主要内容：溶瘤病毒免疫疗法是一个有前途的抗肿瘤策略，在近些年来实现了里程碑式的临床前和临床研究突破。有选择性的、安全的、有效的溶瘤病毒已经在一些新兴的临床前研究中得到发展，其中溶瘤病毒可以用于肿瘤治疗在肿瘤微环境方面遇到的挑战。在此，作者讨论了近期在临床前溶瘤病毒治疗用于解决这方面挑战的研究进展，特别关注的是寻找弥补现有病毒治疗不足、确保最佳的对肿瘤多方面的攻击的新颖策略。这篇综述认为，最有潜力增强溶瘤病毒疗法效应的研究领域：细胞载体、肿瘤血管破坏、微环境调节、联合治疗以及病毒介导的抗肿瘤免疫反应。
附原文摘要：
Oncolyticviruses are a promising anti-cancer platform, achieving significantpre-clinical and clinical milestones in recent years. A full arsenal ofselective, safe, and effective viruses has been developed with some emergingpre-clinical research focusing on optimizing these therapies in the face ofremaining challenges, both in the bloodstream and in the tumourmicroenvironment. Herein we discuss the recent progress in pre-clinicalvirotherapy research to address these challenges, with special focus on innovativestrategies that seek to complement the current strengths of virotherapy,ensuring an optimal multi-faceted attack on cancer. This review highlights theresearch areas that we believe provide the most potential to increase theefficacy of this exciting biotherapy platform: cell carriers, tumour vasculardestruction, microenvironment modulation, combination therapies, andvirus-mediated anti-tumour immune responses.
12、 Oncolytic Viruses for Tumor PrecisionImaging and Radiotherapy
出版物: Human gene therapy（IF2017=4.187，二区）
DOI:10.1089/hum.2017.189
文章类型：综述评论
文章主要内容：Peng等人于2003年在中国发明了表达p53的重组腺病毒（今又生，Gendicine）用于临床肿瘤治疗。这是世界上首个临床批准的基因治疗和肿瘤治疗病毒类药物。一个表达粒细胞-巨噬细胞集落刺激因子溶瘤单纯性疱疹病毒（Talimogenelaherparepvec）于2015年在美国被批准用于治疗黑色素瘤。从那以后，溶瘤病毒在肿瘤治疗学里越来越受到关注，并且在长足发展后成为肿瘤精确成像和放疗的新型有效形式。携带报告基因的溶瘤病毒能够在肿瘤细胞里选择性复制和表达目的基因，因此提高了体外无创的精确分子成像和放疗。这篇文章回顾了在肿瘤成像和放疗中使用溶瘤病毒的最新进展和分子机制，并且给出了后续研究的展望，并且讨论到了多种肿瘤类型，特别关注的是胃肠道肿瘤。
附原文摘要：
In 2003 inChina, Peng et al. invented the recombinant adenovirus expressing p53(Gendicine) for clinical tumor virotherapy. This was the first clinicallyapproved gene therapy and tumor virotherapy drug in the world. An oncolyticherpes simplex virus expressing granulocyte-macrophage colony-stimulatingfactor (Talimogene laherparepvec) was approved for melanoma treatment in theUnited States in 2015. Since then, oncolytic viruses have been attracting moreand more attention in the field of oncology, and may become novel significantmodalities of tumor precision imaging and radiotherapy after furtherimprovement. Oncolytic viruses carrying reporter genes can replicate andexpress genes of interest selectively in tumor cells, thus improving in vivononinvasive precision molecular imaging and radiotherapy. Here, the latestdevelopments and molecular mechanisms of tumor imaging and radiotherapy usingoncolytic viruses are reviewed, and perspectives are given for furtherresearch. Various types of tumors are discussed, and special attention is paidto gastrointestinal tumors.
13、 A Recombinant Antibody-Expressing InfluenzaVirus Delays Tumor Growth in a Mouse Model
出版物: CELL REPORTS（IF2017=8.282，一区）
DOI: 10.1016/j.celrep.2017.12.025
文章类型：研究文章
文章主要内容：流感病毒（IAV）作为溶瘤病毒已经展现出一丝希望。为了让IAV成为一个有效的溶瘤病毒，这个研究设计了一个转基因流感病毒，在病毒复制期间表达一个免疫检查点抑制剂的抗体。为了检验它在感染期间能否表达这个抗体，研究者构建了一个在PB1段编码一个抗体的重链和PA段编码抗体的轻链的流感病毒。这个表达抗体的流感病毒生长到高滴度，并且由感染的细胞分泌的抗体展示出功能上堪比杂交瘤产生的抗体。为了增强IAV的抗肿瘤活性，一个流感病毒被设计出来用于表达一个单链抗体拮抗免疫检查点CTLA4（IAV-CTLA4）。在小鼠中移植恶性的B16-F10黑色素瘤细胞，静脉注射IAV/CTLA4抑制了肿瘤的生长，并且介导了一个远位效应，而且提高了总的生存。
附原文摘要：
Influenza Avirus(IAV) has shown promise as an oncolytic agent. To improve IAV as an oncolyticvirus, we sought to design a transgenic virus expressing an immunecheckpoint-inhibiting antibody during the viral life cycle. To test whether itwas possible to express an antibody during infection, an influenza virus wasconstructed encoding the heavy chain of an antibody on the PB1 segment and thelight chain of an antibody on the PA segment. This antibody-expressing IAVgrows to high titers, and the antibodies secreted from infected cells exhibitcomparable functionality with hybridoma-produced antibodies. To enhance theanti-cancer activity of IAV, an influenza virus was engineered to express asingle-chain antibody antagonizing the immune checkpoint CTLA4 (IAV-CTLA4). Inmice implanted with the aggressive B16-F10 melanoma, intratumoral injectionwith IAVCTLA4 delayed the growth of treated tumors, mediated an abscopaleffect, and increased overall surviva
14、 Multi-modal Potentiation of OncolyticVirotherapy by Vanadium Compounds
出版物: Moleculartherapy : the journal of the American Society of Gene Therapy（IF2017=6.688，一区）
DOI: 10.1016/j.ymthe.2017.10.014
文章类型：研究文章
文章主要内容：溶瘤病毒（OVs）是一种新兴的抗肿瘤生物疗法，它能够通过在肿瘤细胞里选择性复制来诱导抗肿瘤免疫。然而，溶瘤病毒作为单一疗法的疗效是有限的。本研究介绍一种通过结合溶瘤病毒活性和具有免疫调节功能的小分子蛋白酪氨酸磷酸酶抑制剂来增强溶瘤病毒的治疗效果的策略。本研究报告的是钒基磷酸酶抑制剂在化疗耐受的肿瘤细胞系中能增强体外和体内溶瘤病毒的感染。此外，钒化合物联合溶瘤病毒在同源的肿瘤模型中能够增强抗肿瘤免疫疗效，甚至在溶瘤病毒和药物单独难治的模型中引起了全身性和持续性的反应。从机理上看，这个过程涉及到推翻抗病毒的I型干扰素反应进而诱导一个死亡诱导的和促炎的II型干扰素反应，最终导致溶瘤病毒扩散的增加，增强了对肿瘤细胞的杀伤以及增强了抗肿瘤免疫刺激。总的来说，这个研究展现了钒化合物一个新的能力，能够同时最大化病毒的溶瘤作用和全身性的抗肿瘤免疫，为改良的免疫治疗策略的发展提供了新的道路。
附原文摘要：
Oncolytic viruses(OV) are an emerging class of anticancer bio-therapeutics that induce antitumorimmunity through selective replication in tumor cells. However, the efficacy ofOVs as single agents remains limited. We introduce a strategy that boosts thetherapeutic efficacy of OVs by combining their activity with immunomodulating,small molecule protein tyrosine phosphatase inhibitors. We report thatvanadium-based phosphatase inhibitors enhance OV infection invitro and exvivo,in resistant tumor cell lines. Furthermore, vanadium compounds increaseantitumor efficacy in combination with OV in several syngeneic tumor models,leading to systemic and durable responses, even in models otherwise refractoryto OV and drug alone. Mechanistically, this involves subverting the antiviraltype I IFN response toward a death-inducing and pro-inflammatory type II IFNresponse, leading to improved OV spread, increased bystander killing of cancercells, and enhanced antitumor immune stimulation. Overall, we showcase a newability of vanadium compounds to simultaneously maximize viral oncolysis andsystemic anticancer immunity, offering new avenues for the development ofimproved immunotherapy strategies.
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