溶瘤病毒在犬肿瘤治疗中的研究进展

doi:10.16431/j.cnki.1671-7236.2020.03.037

摘要/Abstract

摘要： 溶瘤病毒疗法是利用病毒治疗恶性肿瘤的一种较有前景的新型生物疗法。溶瘤病毒不仅能直接特异性感染和溶解肿瘤细胞，也能刺激肿瘤部位的免疫反应来间接地溶解肿瘤组织细胞，且对正常组织细胞无杀伤或仅有较弱的杀伤作用，从而能达到理想的抗肿瘤效果。文章综述了溶瘤病毒的发展史及溶瘤病毒介导肿瘤消融术的机制，分析麻疹病毒、犬瘟热病毒、新城疫病毒、仙台病毒等8种病毒作为抗肿瘤药物在体外试验、异种移植肿瘤动物模型试验、肿瘤患犬治疗试验等不同阶段对各种犬肿瘤细胞的杀伤效果，提示溶瘤病毒疗法可能是一种安全可靠的恶性肿瘤治疗新方法，但真正将溶瘤病毒疗法应用在犬肿瘤临床治疗中时病毒肿瘤特异性、病毒使用剂量等问题仍需解决，本综述可为溶瘤病毒在犬肿瘤临床治疗中的安全使用提供新的思路和技术途径。

关键词: 溶瘤病毒; 犬肿瘤; 治疗

Abstract: Oncolytic virotherapy is a promising new biological therapy for the treatment of malignant tumors using viruses.The oncolytic virus not only directly infects and dissolves tumor cells,but also stimulates the immune response at the tumor site,to indirectly dissolve the tumor tissue cells,and has no killing or wake killing effect on normal tissue cells,thus achieving satisfying anti-tumor effect.In this paper,the development history of oncolytic virus and the mechanism of tumor ablation mediated by oncolytic virus were reviewed.Then we analyzed the killing effect on various canine tumor cells in vitro,in xenotransplantation tumor animal model and in dogs with tumor of eight oncolytic viruses including measles virus,canine distemper virus,Newcastle disease virus and Sendai virus and so on.Some encouraging results suggested that oncolytic virotherapy might become a safe and reliable new method for the treatment of malignant tumors.However,in order to apply oncolytic virotherapy in the clinical treatment of canine tumors,many problems still need to be solved,such as how to ensure the specificity of the virus,and how to determine the dose of the virus.In summary,this article provided new ideas and technical approaches for the safe use of oncolytic viruses in the clinical treatment of canine tumors.

Key words: oncolytic virus; canine tumor; treatment

中图分类号:

R730.5

任晓丽, 范玉营, 靳双星, 张磊, 刘云, 石冬梅. 溶瘤病毒在犬肿瘤治疗中的研究进展[J]. 中国畜牧兽医, 2020, 47(3): 965-971.

REN Xiaoli, FAN Yuying, JIN Shuangxing, ZHANG Lei, LIU Yun, SHI Dongmei. Research Progress on Oncolytic Viruses in Canine Tumor Treatment[J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(3): 965-971.

参考文献

[1] BAIONI E,SCANZIANI E,VINCENTI M C,et al.Estimating canine cancer incidence:Findings from a population-based tumour registry in northwestern Italy[J].BMC Veterinary Research,2017,13(1):203.
[2] ROMANO G,MARINO I R.Abscopal effects observed in cancer radiation therapy and oncolytic virotherapy:An overview[J].Drugs Today (Barc),2019,55(2):117-130.
[3] BLUMING A Z,ZIEGLER J L.Regression of Burkitt's lymphoma in association with measles infection[J].Lancet,1971,2(7715):105-106.
[4] BIERMAN H R,CRILE D M,DOD K S,et al.Remissions in leukemia of childhood following acute infectious disease:Staphylococcus and Streptococcus,varicella,and feline panleukopenia[J].Cancer,1953,6(3):591-605.
[5] HUEBNER R J,ROWE W P,SCHATTEN W E,et al.Studies on the use of viruses in the treatment of carcinoma of the cervix[J].Cancer,1956,9(6):1211-1218.
[6] SOUTHAM C M,MOORE A E.Clinical studies of viruses as antineoplastic agents with particular reference to Egypt 101 virus[J].Cancer,1952,5(5):1025-1034.
[7] GARBER K.China approves world's first oncolytic virus therapy for cancer treatment[J].Journal of the National Cancer Institute,2006,98(5):298-300.
[8] ELIE D.Oncolytic viruses get a boost with first FDA-approval recommendation[J].Nature Reviews Drug Discovery,2015,14(6)369-371.
[9] FU L Q,WANG S B,CAI M H,et al.Recent advances in oncolytic virus-based cancer therapy[J].Virus Research,2019,270:197675.
[10] BREITBACH C J,ARULANANDAM R,DE SILVA N,et al.Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans[J].Cancer Research,2013,73(4):1265-1275.
[11] ADELFINGER M,BESSLER S,FRENTZEN A,et al.Preclinical testing oncolytic vaccinia virus strain GLV-5b451 expressing an anti-VEGF single-chain antibody for canine cancer therapy[J].Viruses,2015,7(7):4075-4092.
[12] LE BOEUF F,SELMAN M,SON H H,et al.Oncolytic maraba virus MG1 as a treatment for sarcoma[J].International Journal of Cancer,2017,141(6):1257-1264.
[13] BOMMAREDDY P K,SHETTIGAR M,KAUFMAN H L.Integrating oncolytic viruses in combination cancer immunotherapy[J].Nature Reviews Immunology,2018,18(8):498-513.
[14] MARCHINI A,DAEFFLER L,POZDEEV V I,et al.Immune conversion of tumor microenvironment by oncolytic viruses:The protoparvovirus H-1PV case study[J].Frontiers in Immunology,2019,10:1848.
[15] MELL L K,BRUMUND K T,DANIELS G A,et al.Phase Ⅰ trial of intravenous oncolytic vaccinia virus (GL-ONC1) with cisplatin and radiotherapy in patients with locoregionally advanced head and neck carcinoma[J].Clinical Cancer Research,2017,23(19):5696-5702.
[16] IGASE M,SHIBUTANI S,KUROGOUCHI Y,et al.Combination therapy with reovirus and ATM inhibitor enhances cell death and virus replication in canine melanoma[J].Molecular Therapy-Oncolytics,2019,15:49-59.
[17] HUANG H,LIU Y,LIAO W,et al.Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapy[J].Nature Communications,2019,10(1):4801.
[18] ZYGIERT Z.Hodgkin's disease:Remissions after measles[J].Lancet,1971,1(7699):593.
[19] TAQI A M,ABDURRAHMAN M B,YAKUBU A M,et al.Regression of Hodgkin's disease after measles[J].Lancet,1981,1(8229):1112.
[20] SINGH B K,HORNICK A L,KRISHNAMURTHY S,et al.The nectin-4/afadin protein complex and intercellular membrane pores contribute to rapid spread of measles virus in primary human airway epithelia[J].Journal of Virology,2015,89(14):7089-7096.
[21] DERYCKE M S,PAMBUCCIAN S E,GILKS C B,et al.Nectin 4 overexpression in ovarian cancer tissues and serum:Potential role as a serum biomarker[J].American Journal of Clinical Pathology,2010,134(5):835-845.
[22] SHOJI K,YONEDA M,FUJIYUKI T,et al.Development of new therapy for canine mammary cancer with recombinant measles virus[J].Molecular Therapy-Oncolytics,2016,3:15022.
[23] KHOSRAVI M,BRINGOLF F,ROTHLISBERGER S,et al.Canine distemper virus fusion activation:Critical role of residue E123 of CD150/SLAM[J].Journal of Virology,2016,90(3):1622-1637.
[24] DEL P H,MARTINS A S,MILSTED A,et al.Canine distemper virus induces apoptosis in cervical tumor derived cell lines[J].Virology Journal,2011,8:334.
[25] SUTER S E,CHEIN M B,VON MESSLING V,et al.In vitro canine distemper virus infection of canine lymphoid cells:A prelude to oncolytic therapy for lymphoma[J].Clinical Cancer Research,2005,11(4):1579-1587.
[26] GARCIA J A,FERREIRA H L,VIEIRA F V,et al.Tumour necrosis factor-alpha-induced protein 8(TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus[J].Veterinary and Comparative Oncology,2017,15(2):336-344.
[27] GRONE A,FONFARA S,BAUMGARTNER W.Cell type-dependent cytokine expression after canine distemper virus infection[J].Viral Immunology,2002,15(3):493-505.
[28] YAMAGUCHI R,KOJIMOTO A,SAKAI H,et al.Growth characteristics of canine distemper virus in a new cell line CCT cells originated from canine malignant histiocytosis[J].Journal of Veterinary Medical Science,2005,67(2):203-206.
[29] DERVISIS N G,KIUPEL M,QIN Q,et al.Clinical prognostic factors in canine histiocytic sarcoma[J].Veterinary and Comparative Oncology,2017,15(4):1171-1180.
[30] FORD R B,LARSON L J,MCCLURE K D,et al.2017 AAHA canine vaccination guidelines[J].Journal of the American Animal Hospital Association,2017,53(5):243-251.
[31] LI P,WANG J,CHEN G,et al.Oncolytic activity of canine distemper virus in canine mammary tubular adenocarcinoma cells[J].Veterinary and Comparative Oncology,2019,17(2):174-183.
[32] SANCHEZ D,PELAYO R,MEDINA L A,et al.Newcastle disease virus:Potential therapeutic application for human and canine lymphoma[J].Viruses,2015,8(1)E3.
[33] KOKS C A,GARG A D,EHRHARDT M,et al.Newcastle disease virotherapy induces long-term survival and tumor-specific immune memory in orthotopic glioma through the induction of immunogenic cell death[J].International Journal of Cancer,2015,136(5):E313-E325.
[34] ILYINSKAYA G V,MUKHINA E V,SOBOLEVA A V,et al.Oncolytic Sendai virus therapy of canine mast cell tumors (a pilot study)[J].Frontiers in Veterinary Science,2018,5:116.
[35] DONNELLY L,MULLIN C,BALKO J,et al.Evaluation of histological grade and histologically tumour-free margins as predictors of local recurrence in completely excised canine mast cell tumours[J].Veterinary and Comparative Oncology,2015,13(1):70-76.
[36] NAIK S,GALYON G D,JENKS N J,et al.Comparative oncology evaluation of intravenous recombinant oncolytic vesicular stomatitis virus therapy in spontaneous canine cancer[J].Molecular Cancer Therapeutics,2018,17(1):316-326.
[37] LEBLANC A K,NAIK S,GALYON G D,et al.Safety studies on intravenous administration of oncolytic recombinant vesicular stomatitis virus in purpose-bred beagle dogs[J].Human Gene Therapy Clinical Development,2013,24(4):174-181.
[38] SHEN W,PATNAIK M M,RUIZ A,et al.Immunovirotherapy with vesicular stomatitis virus and PD-L1 blockade enhances therapeutic outcome in murine acute myeloid leukemia[J].Blood,2016,127(11):1449-1458.
[39] KIMPEL J,URBIOLA C,KOSKE I,et al.The oncolytic virus VSV-GP is effective against malignant melanoma[J].Viruses,2018,10(3):E108.
[40] HWANG C C,MOCHIZUKI M,MAEDA K,et al.Seroepidemiology of reovirus in healthy dogs in six prefectures in Japan[J].Journal of Veterinary Medical Science,2014,76(3):471-475.
[41] GONG J,SACHDEV E,MITA A C,et al.Clinical development of reovirus for cancer therapy:An oncolytic virus with immune-mediated antitumor activity[J].World Journal of Methodology,2016,6(1):25-42.
[42] HWANG C C,UMEKI S,IGASE M,et al.The effects of oncolytic reovirus in canine lymphoma cell lines[J].Veterinary and Comparative Oncology,2016,14(Suppl 1):61-73.
[43] IGASE M,SHOUSU K,FUJIKI N,et al.Anti-tumour activity of oncolytic reovirus against canine histiocytic sarcoma cells[J].Veterinary and Comparative Oncology,2019,17(2):184-193.
[44] NORMAN K L,HIRASAWA K,YANG A D,et al.Reovirus oncolysis:The Ras/RalGEF/p38 pathway dictates host cell permissiveness to reovirus infection[J].Proceeding of the National of the United States of America,2004,101(30):11099-11104.
[45] IGASE M,HWANG C C,COFFEY M,et al.The oncolytic effects of reovirus in canine solid tumor cell lines[J].Journal of Veterinary Medical Science,2015,77(5):541-548.
[46] HWANG C C,IGASE M,SAKURAI M,et al.Oncolytic reovirus therapy:Pilot study in dogs with spontaneously occurring tumours[J].Veterinary and Comparative Oncology,2018,16(2):229-238.
[47] FREY S E,NEWMAN F K,CRUZ J,et al.Dose-related effects of smallpox vaccine[J].New England Journal of Medicine,2002,346(17):1275-1280.
[48] GENTSCHEV I,EHRIG K,DONAT U,et al.Significant growth inhibition of canine mammary carcinoma xenografts following treatment with oncolytic vaccinia virus GLV-1h68[J].Journal of Oncology,2010,2010:736907.
[49] GENTSCHEV I,ADELFINGER M,JOSUPEIT R,et al.Preclinical evaluation of oncolytic vaccinia virus for therapy of canine soft tissue sarcoma[J].PLoS One,2012,7(5):e37239.
[50] PATIL S S,GENTSCHEV I,ADELFINGER M,et al.Virotherapy of canine tumors with oncolytic vaccinia virus GLV-1h109 expressing an anti-VEGF single-chain antibody[J].PLoS One,2012,7(10):e47472.
[51] GENTSCHEV I,PATIL S S,ADELFINGER M,et al.Characterization and evaluation of a new oncolytic vaccinia virus strain LIVP6.1.1 for canine cancer therapy[J].Bioengineered,2013,4(2):84-89.
[52] ALCAYAGA-MIRANDA F,CASCALLO M,ROJAS J J,et al.Osteosarcoma cells as carriers to allow antitumor activity of canine oncolytic adenovirus in the presence of neutralizing antibodies[J].Cancer Gene Therapy,2010,17(11):792-802.
[53] LABORDA E,PUIG-SAUS C,RODRIGUEZ-GARCIA A,et al.A pRb-responsive,RGD-modified,and hyaluronidase-armed canine oncolytic adenovirus for application in veterinary oncology[J].Molecular Therapy,2014,22(5):986-998.
[54] CEJALVO T,PERISE-BARRIOS A J,DEL P I,et al.Remission of spontaneous canine tumors after systemic cellular viroimmunotherapy[J].Cancer Research,2018,78(17):4891-4901.
[55] TERNOVOI V V,LE L P,BELOUSOVA N,et al.Productive replication of human adenovirus type 5 in canine cells[J].Journal of Virology,2005,79(2):1308-1311.
[56] WESTBERG S,SADEGHI A,SVENSSON E,et al.Treatment efficacy and immune stimulation by AdCD40L gene therapy of spontaneous canine malignant melanoma[J].Journal of Immunotherapy,2013,36(6):350-358.