鼻咽癌疫苗的研究进展
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摘要
鼻咽癌(nasopharyngeal carcinoma,NPC)是我国南方地区最常见的恶性肿瘤之一,研究表明,其病因与EB病毒(Epstein-Barr virus,EBV)的感染密切相关。本文旨在对鼻咽癌、EBV、鼻咽癌诊断和治疗现状进行简要综述,并对国内外鼻咽癌相关预防和治疗性疫苗的研究现状进行概述,对未来相关疫苗的研究方向进行展望。
Nasopharyngeal carcinoma(NPC) is one of the most common malignant tumor in the south of China. Researches show that the tumor is statistically related to Epstein-Barr virus(EBV). The article introduces NPC,EBV as well as the current situation of diagnosis and treatment of NPC,while emphasis on the prospect of preventive and therapeutic vaccines.
Nasopharyngeal carcinoma(NPC) is one of the most common malignant tumor in the south of China. Researches show that the tumor is statistically related to Epstein-Barr virus(EBV). The article introduces NPC,EBV as well as the current situation of diagnosis and treatment of NPC,while emphasis on the prospect of preventive and therapeutic vaccines.
引文
[1]TSAO S W,YIP Y L,TSANG C M,et al.Etiological factors of nasopharyngeal carcinoma[J].Oral Oncol,2014,50(5):330-338.
[2]ZHANG L X.Study of immunologic effect of recombinant MVAvirus of expressing EBV-LMP2[D].Beijing:Beijing University of Technology,2014.(in Chinese)张丽霞.EBV-LMP2重组痘苗病毒免疫效果研究[D].北京:北京工业大学,2014.
[3]ZHAO S P.Basic&Clinical Nasopharyngeal carcinoma[M].Changsha:Hunan Science&Technology Press,2012.(in Chinese)赵素萍.鼻咽癌基础与临床[M].湖南长沙:湖南科学技术出版社,2012.
[4]CHEN Y Q,LI Z X,HU B,et al.Construction of recombinant plasmids of VCA protein P23 of Epstein-Barr virus and its expression in Pichia pastoris[J].China J Mod Med,2012,22(29):11-15.(in Chinese)陈亚琼,李朝霞,胡波,等.EB病毒衣壳蛋白P23重组质粒的构建及其在毕赤酵母中的表达[J].中国现代医学杂志,2012,22(29):11-15.
[5]WEI B,GU S Y.Immunotherapy and vaccine strategies against Epstein-Barr virus-associated diseases[J].Lett in Biotechnol,2001,12(4):302-309.(in Chinese)魏滨,谷淑燕.Epstein-Barr病毒相关疾病的免疫治疗与疫苗发展策略[J].生物技术通讯,2001,12(4):302-309.
[6]ZOU J H,WAN X C,WANG P.New progress on Epstein-Barr virus vaccine research[J].Prog in Mod Biomed,2015,15(3):543-546.(in Chinese)邹军辉,万晓春,王蒲.EB病毒疫苗的研究进展[J].现代生物医学进展,2015,15(3):543-546.
[7]JIANG P Z,SHEN X M,HUANG H,et al.Infection of immortalized human epithelial cell line Hacat with high-concentration Epstein-Barr virus[J].J First Mil Med Univ,2002,22(11):970-973.(in Chinese)江培洲,沈新明,黄华,等.高浓度EB病毒感染人永生化上皮细胞Hacat系[J].第一军医大学学报,2002,22(11):970-973.
[8]SHANNON-LOWE C,ROWE M.Epstein Barr virus entry;kissing and conjugation[J].Curr Opin Virol,2014,4(1):78-84.
[9]SHANNON-LOWE C,ROWE M.Epstein-Barr virus infection of polarized epithelial cells via the basolateral surface by memory B cell-mediated transfer infection[J].PLoS Pathog,2011,7(5):e1001338.doi:10.1371/journal.ppat.1001338.
[10]JIANG P Z,SHEN X M,LV L C,et al.Cell-to-cell contacting is an effective pathway for Epstein-Barr virus to spontaneously infect human epithelial cells[J].Virol Sin,2004,19(1):1-5.(in Chinese)江培洲,沈新明,吕丽春,等.细胞间接触是EB病毒自发感染人类上皮细胞的有效途径[J].中国病毒学,2004,19(1):1-5.
[11]GARCIA N J,CHEN J,LONGNECKER R.Modulation of Epstein-Barr virus glycoprotein B(gB)fusion activity by the gBcytoplasmic tail domain[J].Mbio,2013,4(1):e00571-12.doi:10.1128/mBio.00571-12.
[12]JIN W,LI C,DU T,et al.DC-SIGN plays a stronger role than DCIR in mediating HIV-1 capture and transfer[J].Virology,2014,458-459(1):83-92.
[13]ZHANG N,HU C H.Effects of EB virus and host immune in the pathogenesis of nasopharyngeal carcinoma and the progress of relative immune therapy[J].Chin Clin Oncol,2017,22(2):184-188.(in Chinese)张娜,胡春宏.EB病毒与宿主免疫在鼻咽癌发病中的作用及相关免疫治疗的研究进展[J].临床肿瘤学杂志,2017,22(2):184-188.
[14]吴若实,农胜利.EB病毒与鼻咽癌发生发展关系的研究进展[J].现代医药卫生,2016,32(14):2182-2184.
[15]WU J X,HE J Y,DU K X,et al.Detection of circulating tumor cells in peripheral blood of patients with nasopharyngeal carcinoma and evaluate its prognostic value[J].Mod Oncol,2017,25(7):1035-1039.(in Chinese)吴君心,贺俊彦,杜开新,等.鼻咽癌患者外周血循环肿瘤细胞的检测及其与预后的相关性[J].现代肿瘤医学,2017,25(7):1035-1039.
[16]YE Q,LI X L,CHEN Y S,et al.Diagnostic value of serological Epstein-Barr viral antibodies and Epstein-Barr viral DNAassays in the management of nasopharyngeal carcinoma[J].Mod Oncol,2016,24(19):3045-3048.(in Chinese)叶倩,李筱莉,陈岩松,等.联合检测EB病毒不同抗体及EB病毒DNA在鼻咽癌血清学诊断中的价值[J].现代肿瘤医学,2016,24(19):3045-3048.
[17]PAN J Z,HUANG H S,ZHU Y X,et al.Clinical value of three kinds of EB virus antibody detection in screening of nasopharyngeal carcinoma[J].China Med Pharm,2016,6(19):2225-228.(in Chinese)潘继钊,黄海深,朱苑霞,等.探讨三种EB病毒抗体检测在鼻咽癌筛查中的临床价值[J].中国医药科学,2016,6(19):225-228.
[18]马钊恩,刘晓清,冀天星,等.血清EB病毒衣壳抗原IgA检测在鼻咽癌辅助诊断中的价值[J].检验医学与临床,2017,14(6):830-831.
[19]HSIAO J R,JIN Y T,TSAI S T.Detection of cell free EpsteinBarr virus DNA in sera from patients with nasopharynegeal carcinoma[J].Cancer,2002,94(3):723-729.
[20]LIN L W.Research progress of EB virus DNA test in diagnosis of nasopharyngeal carcinoma[J].World Latest Med Inform(Elect Version),2017,17(31):42-43.(in Chinese)林丽文.EB病毒DNA检测在鼻咽癌诊疗中的研究进展[J].世界最新医学信息文摘,2017,17(31):42-43.
[21]QIU H K,YAO Y C,LI L,et al.Combined detection of Epstein-Barr virus-related antibodies and EBV DNA for nasopharyngeal carcinoma early diagnosis[J].Lab Med Clin,2015,12(10):1339-1344.(in Chinese)邱厚匡,姚亚超,李磊,等.EB病毒抗体及其DNA联合检测在鼻咽癌筛查和早期诊断中的价值[J].检验医学与临床,2015,12(10):1339-1344.
[22]赵芫,孙云鹏.血清EB病毒VCA-IgA、CEA及SF联合检测在鼻咽癌诊断中的应用价值[J].临床合理用药,2017,10(9A):157-159.
[23]WANG M.Expression and immunogenicity study of human enterovirus 71 and Epstein-Barr virus vaccine candidate antigens in Pichia pastoris[D].Wuhan:Wuhan University,2014.(in Chinese)王曼.人类肠道病毒71型与EB病毒疫苗候选抗原在毕赤酵母中的表达及免疫原性研究[D].湖北武汉:武汉大学,2014.
[24]EPSTEIN M A.Epstein-Barr virus-is it time to develop a vaccine program[J].Natl Cancer Inst,1976,56(4):697-700.
[25]MOUTSCHEN M,LEONARD P,SOKAL E M,et al.Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults[J].Vaccine,2007,25(24):4697-4705.
[26]CUI X,CAO Z,SEN G,et al.A novel tetrameric gp3501-470as a potential Epstein-Barr virus vaccine[J].Vaccine,2013,31(30):3039-3045.
[27]TONG Y Y,LI H X,ZHANG L X,et al.Construction and immunological responses of recombinant adenovirus containing Epstein-Barr nuclear antigen 1 in mice[J].Chin J Virol,2014,30(4):429-435.(in Chinese)仝艳艳,李红霞,张丽霞,等.含EB病毒核抗原1重组腺病毒的构建及其在小鼠中免疫效果研究[J].病毒学报,2014,30(4):429-435.
[28]周玲,李德锐,王琦,等.鼻咽癌治疗和预防性疫苗[J].中国科技成果,2008,9(5):49-49.
[29]SMITH C,TSANG J,BEAGLEY L,et al.Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy[J].Cancer Res,2012,72(5):1116-1125.
[30]TAYLOR G S,JIA H,HARRINGTON K,et al.A recombinant modified vaccinia Ankara vaccine encoding epstein-barr virus(EBV)target antigens:A phase I trial in UK patients with EBV positive cancer[J].Clin Cancer Res,2014,20(19):5009-5022.
[31]WANG Z,ZHOU L,WU X B,et al.Immune responses in rhesus induced by recombinant adenovirus Ad-LMP2[J].Chin JExp Clin Virol,2006,20(2):63-65.(in Chinese)王湛,周玲,吴小兵,等.Ad-LMP2重组腺病毒疫苗在恒河猴体内免疫效果的研究[J].中华实验和临床病毒学杂志,2006,20(2):63-65.
[32]王湛,孙云霞,周玲,等.EBV-LMP2重组腺病毒体内细胞免疫效果及分布研究[J].中国医药指南,2010,8(16):66-69.
[33]ZHAO W,CHEN X Q,WAN X,et al.Construction of LmddLMP2A,an attenuated Listeria vaccine strain expressing the Epstein-Barr virus latent membrane protein 2A(EBV-LMP2A)and evaluation of its anti-tumor effects against nasopharyngeal carcinoma[J].Chin J Microbiol Immunol,2015,35(3):207-212.(in Chinese)赵玮,陈小琴,万昕,等.鼻咽癌特异性减毒重组疫苗Lmdd-LMP2A的构建及其抑瘤效应的研究[J].中华微生物学和免疫学杂志,2015,35(3):207-212.
[2]ZHANG L X.Study of immunologic effect of recombinant MVAvirus of expressing EBV-LMP2[D].Beijing:Beijing University of Technology,2014.(in Chinese)张丽霞.EBV-LMP2重组痘苗病毒免疫效果研究[D].北京:北京工业大学,2014.
[3]ZHAO S P.Basic&Clinical Nasopharyngeal carcinoma[M].Changsha:Hunan Science&Technology Press,2012.(in Chinese)赵素萍.鼻咽癌基础与临床[M].湖南长沙:湖南科学技术出版社,2012.
[4]CHEN Y Q,LI Z X,HU B,et al.Construction of recombinant plasmids of VCA protein P23 of Epstein-Barr virus and its expression in Pichia pastoris[J].China J Mod Med,2012,22(29):11-15.(in Chinese)陈亚琼,李朝霞,胡波,等.EB病毒衣壳蛋白P23重组质粒的构建及其在毕赤酵母中的表达[J].中国现代医学杂志,2012,22(29):11-15.
[5]WEI B,GU S Y.Immunotherapy and vaccine strategies against Epstein-Barr virus-associated diseases[J].Lett in Biotechnol,2001,12(4):302-309.(in Chinese)魏滨,谷淑燕.Epstein-Barr病毒相关疾病的免疫治疗与疫苗发展策略[J].生物技术通讯,2001,12(4):302-309.
[6]ZOU J H,WAN X C,WANG P.New progress on Epstein-Barr virus vaccine research[J].Prog in Mod Biomed,2015,15(3):543-546.(in Chinese)邹军辉,万晓春,王蒲.EB病毒疫苗的研究进展[J].现代生物医学进展,2015,15(3):543-546.
[7]JIANG P Z,SHEN X M,HUANG H,et al.Infection of immortalized human epithelial cell line Hacat with high-concentration Epstein-Barr virus[J].J First Mil Med Univ,2002,22(11):970-973.(in Chinese)江培洲,沈新明,黄华,等.高浓度EB病毒感染人永生化上皮细胞Hacat系[J].第一军医大学学报,2002,22(11):970-973.
[8]SHANNON-LOWE C,ROWE M.Epstein Barr virus entry;kissing and conjugation[J].Curr Opin Virol,2014,4(1):78-84.
[9]SHANNON-LOWE C,ROWE M.Epstein-Barr virus infection of polarized epithelial cells via the basolateral surface by memory B cell-mediated transfer infection[J].PLoS Pathog,2011,7(5):e1001338.doi:10.1371/journal.ppat.1001338.
[10]JIANG P Z,SHEN X M,LV L C,et al.Cell-to-cell contacting is an effective pathway for Epstein-Barr virus to spontaneously infect human epithelial cells[J].Virol Sin,2004,19(1):1-5.(in Chinese)江培洲,沈新明,吕丽春,等.细胞间接触是EB病毒自发感染人类上皮细胞的有效途径[J].中国病毒学,2004,19(1):1-5.
[11]GARCIA N J,CHEN J,LONGNECKER R.Modulation of Epstein-Barr virus glycoprotein B(gB)fusion activity by the gBcytoplasmic tail domain[J].Mbio,2013,4(1):e00571-12.doi:10.1128/mBio.00571-12.
[12]JIN W,LI C,DU T,et al.DC-SIGN plays a stronger role than DCIR in mediating HIV-1 capture and transfer[J].Virology,2014,458-459(1):83-92.
[13]ZHANG N,HU C H.Effects of EB virus and host immune in the pathogenesis of nasopharyngeal carcinoma and the progress of relative immune therapy[J].Chin Clin Oncol,2017,22(2):184-188.(in Chinese)张娜,胡春宏.EB病毒与宿主免疫在鼻咽癌发病中的作用及相关免疫治疗的研究进展[J].临床肿瘤学杂志,2017,22(2):184-188.
[14]吴若实,农胜利.EB病毒与鼻咽癌发生发展关系的研究进展[J].现代医药卫生,2016,32(14):2182-2184.
[15]WU J X,HE J Y,DU K X,et al.Detection of circulating tumor cells in peripheral blood of patients with nasopharyngeal carcinoma and evaluate its prognostic value[J].Mod Oncol,2017,25(7):1035-1039.(in Chinese)吴君心,贺俊彦,杜开新,等.鼻咽癌患者外周血循环肿瘤细胞的检测及其与预后的相关性[J].现代肿瘤医学,2017,25(7):1035-1039.
[16]YE Q,LI X L,CHEN Y S,et al.Diagnostic value of serological Epstein-Barr viral antibodies and Epstein-Barr viral DNAassays in the management of nasopharyngeal carcinoma[J].Mod Oncol,2016,24(19):3045-3048.(in Chinese)叶倩,李筱莉,陈岩松,等.联合检测EB病毒不同抗体及EB病毒DNA在鼻咽癌血清学诊断中的价值[J].现代肿瘤医学,2016,24(19):3045-3048.
[17]PAN J Z,HUANG H S,ZHU Y X,et al.Clinical value of three kinds of EB virus antibody detection in screening of nasopharyngeal carcinoma[J].China Med Pharm,2016,6(19):2225-228.(in Chinese)潘继钊,黄海深,朱苑霞,等.探讨三种EB病毒抗体检测在鼻咽癌筛查中的临床价值[J].中国医药科学,2016,6(19):225-228.
[18]马钊恩,刘晓清,冀天星,等.血清EB病毒衣壳抗原IgA检测在鼻咽癌辅助诊断中的价值[J].检验医学与临床,2017,14(6):830-831.
[19]HSIAO J R,JIN Y T,TSAI S T.Detection of cell free EpsteinBarr virus DNA in sera from patients with nasopharynegeal carcinoma[J].Cancer,2002,94(3):723-729.
[20]LIN L W.Research progress of EB virus DNA test in diagnosis of nasopharyngeal carcinoma[J].World Latest Med Inform(Elect Version),2017,17(31):42-43.(in Chinese)林丽文.EB病毒DNA检测在鼻咽癌诊疗中的研究进展[J].世界最新医学信息文摘,2017,17(31):42-43.
[21]QIU H K,YAO Y C,LI L,et al.Combined detection of Epstein-Barr virus-related antibodies and EBV DNA for nasopharyngeal carcinoma early diagnosis[J].Lab Med Clin,2015,12(10):1339-1344.(in Chinese)邱厚匡,姚亚超,李磊,等.EB病毒抗体及其DNA联合检测在鼻咽癌筛查和早期诊断中的价值[J].检验医学与临床,2015,12(10):1339-1344.
[22]赵芫,孙云鹏.血清EB病毒VCA-IgA、CEA及SF联合检测在鼻咽癌诊断中的应用价值[J].临床合理用药,2017,10(9A):157-159.
[23]WANG M.Expression and immunogenicity study of human enterovirus 71 and Epstein-Barr virus vaccine candidate antigens in Pichia pastoris[D].Wuhan:Wuhan University,2014.(in Chinese)王曼.人类肠道病毒71型与EB病毒疫苗候选抗原在毕赤酵母中的表达及免疫原性研究[D].湖北武汉:武汉大学,2014.
[24]EPSTEIN M A.Epstein-Barr virus-is it time to develop a vaccine program[J].Natl Cancer Inst,1976,56(4):697-700.
[25]MOUTSCHEN M,LEONARD P,SOKAL E M,et al.Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults[J].Vaccine,2007,25(24):4697-4705.
[26]CUI X,CAO Z,SEN G,et al.A novel tetrameric gp3501-470as a potential Epstein-Barr virus vaccine[J].Vaccine,2013,31(30):3039-3045.
[27]TONG Y Y,LI H X,ZHANG L X,et al.Construction and immunological responses of recombinant adenovirus containing Epstein-Barr nuclear antigen 1 in mice[J].Chin J Virol,2014,30(4):429-435.(in Chinese)仝艳艳,李红霞,张丽霞,等.含EB病毒核抗原1重组腺病毒的构建及其在小鼠中免疫效果研究[J].病毒学报,2014,30(4):429-435.
[28]周玲,李德锐,王琦,等.鼻咽癌治疗和预防性疫苗[J].中国科技成果,2008,9(5):49-49.
[29]SMITH C,TSANG J,BEAGLEY L,et al.Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy[J].Cancer Res,2012,72(5):1116-1125.
[30]TAYLOR G S,JIA H,HARRINGTON K,et al.A recombinant modified vaccinia Ankara vaccine encoding epstein-barr virus(EBV)target antigens:A phase I trial in UK patients with EBV positive cancer[J].Clin Cancer Res,2014,20(19):5009-5022.
[31]WANG Z,ZHOU L,WU X B,et al.Immune responses in rhesus induced by recombinant adenovirus Ad-LMP2[J].Chin JExp Clin Virol,2006,20(2):63-65.(in Chinese)王湛,周玲,吴小兵,等.Ad-LMP2重组腺病毒疫苗在恒河猴体内免疫效果的研究[J].中华实验和临床病毒学杂志,2006,20(2):63-65.
[32]王湛,孙云霞,周玲,等.EBV-LMP2重组腺病毒体内细胞免疫效果及分布研究[J].中国医药指南,2010,8(16):66-69.
[33]ZHAO W,CHEN X Q,WAN X,et al.Construction of LmddLMP2A,an attenuated Listeria vaccine strain expressing the Epstein-Barr virus latent membrane protein 2A(EBV-LMP2A)and evaluation of its anti-tumor effects against nasopharyngeal carcinoma[J].Chin J Microbiol Immunol,2015,35(3):207-212.(in Chinese)赵玮,陈小琴,万昕,等.鼻咽癌特异性减毒重组疫苗Lmdd-LMP2A的构建及其抑瘤效应的研究[J].中华微生物学和免疫学杂志,2015,35(3):207-212.