用于癌症免疫疗法的慢病毒载体的研究进展
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摘要
近年来,得益于对癌症免疫监视和逃逸机制理解的不断深入及基因转运载体的发展,免疫疗法在临床上取得了一系列的成功。本文将介绍包括慢病毒载体(lentivirus,LV)的基本结构和生活史在内的发展历程。LV应用中的最主要安全性风险来源于具有复制能力的慢病毒载体(replication competent LV,RCL),针对这一问题发展出了一系列新的LV和相应的辅助手段。目前作为癌症免疫疗法主流的过继细胞传输法包括T细胞受体(T cell receptor,TCR)-T细胞和嵌合抗原受体(chimeric antigen receptor,CAR)-T细胞疗法,其中LV已被广泛应用。此外本文还针对LV应用中的一些监管方面的问题及LV的未来发展方向进行探讨。
Recently,due to the advancement in understanding of mechanism of immunological surveillance and escape of cancer as well as the development of gene delivery vector,immunotherapy achieved a number of clinical success. In this review we will overview the progress in research on lentivirus(LV) including its basic structure and life cycle. The main issue of lentivirus in safety comes from the replication competent LV(RCL),therefore iteration vector and other approaches have been developed. Nowadays,LV has been broadly used in the adoptive T-cell transfer therapy,the mainstream of cancer immunotherapy,such as T cell receptor(TCR)-T therapy and chimeric antigen receptor(CAR)-T therapy. The problem in regulation and the future direction of LV vector are also discussed.
Recently,due to the advancement in understanding of mechanism of immunological surveillance and escape of cancer as well as the development of gene delivery vector,immunotherapy achieved a number of clinical success. In this review we will overview the progress in research on lentivirus(LV) including its basic structure and life cycle. The main issue of lentivirus in safety comes from the replication competent LV(RCL),therefore iteration vector and other approaches have been developed. Nowadays,LV has been broadly used in the adoptive T-cell transfer therapy,the mainstream of cancer immunotherapy,such as T cell receptor(TCR)-T therapy and chimeric antigen receptor(CAR)-T therapy. The problem in regulation and the future direction of LV vector are also discussed.
引文
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[14]CARMINE C,MILONE M C,RAFFIT H,et al.Control of large,established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains[J].Proc Ntl Acad Sci USA,2009,106(9):3360-3365.
[15]MARKUS C,CAROLINE K,HOMBACH A A,et al.IL-12release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression[J].Cancer Res,2011,71(17):5697.
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[18]Products CfPM.Editor note for guidance on the quality,preclinical and clinical aspects of gene transfer medicinal products[S].London:The European Agency for the Evaluation of Medicinal Products,2001.
[19]CHEN J,REEVES L,CORNETTA K.Safety testing for replication-competent retrovirus associated with gibbon ape leukemia virus-pseudotyped retroviral vectors[J].Hum Gene Ther,2001,12(1):61-70.
[20]Administration UFaD.Guidance for industry:supplemental guidance on testing for replication competent retrovirus in retroviral vector based gene therapy products and during follow-up of patients in clinical trials using retroviral vectors[OL].(2001-11-14)[2018-11-17].http://www.fda.gov/Biologics-BloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Cellulara.
[21]STEPHANIE P,CHAMSY S,MARTINE B,et al.Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo[J].Proc Natl Acad Sci USA,2006,103(47):17684-17689.
[22]KATARZYNA K,SAYANDIP M,LUIS A,et al.Nonintegrating lentivector vaccines stimulate prolonged T-cell and antibody responses and are effective in tumor therapy[J].J Virol,2009,83(7):3094.
[23]CORNU T I,CATHOMEN T.Targeted genome modifications using integrase-deficient lentiviral vectors[J].Mol Ther,2007,15(12):2107-2113.
[24]GRANDCHAMP N,ALTEMIR D,PHILIPPE S,et al.Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage[J].PloS One,2014,9(6):e99649.
[2]BRECKPOT K,AERTS J L,THILEMANS K.Lentiviral vectors for cancer immunotherapy:transforming infectious particles into therapeutics[J].Gene Ther,2007,14(11):847-862.
[3]ESCORS D,BRECKPOT K.Lentiviral vectors in gene therapy:their current status and future potential[J].Arch Immunol et Ther Exp,2010,58(2):107-119.
[4]GINN S L,ALEXANDER I E,EDELSTEIN M L,et al.Gene therapy clinical trials worldwide to 2012-an update[J].J Gene Med,2013,15(2):65-77.
[5]GINN S L,AMAYA A K,ALEXANDER I E,et al.Gene therapy clinical trials worldwide to 2017:an update[J].J Med,2018,20(5):e3015.
[6]MALIM M H,EMERMAN M.HIV-1 accessory proteins-ensuring viral survival in a hostile environment[J].Cell Host&Microbe,2008,3(6):388-398.
[7]PALU G,PAROLIN C,TAKEUCHI Y,et al.Progress with retroviral gene vectors[J].Rev Med Virol,2015,10(3):185-202.
[8]YANG S,COHEN C,ZHAO Y,et al.Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition[J].Gene Ther,2008,15(21):1411.
[9]BENDLE G M,LINNEMANN CHOOIJKAAS A I,BIES L,et al.Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy[J].Nat Med,2010,16(5):565-570.
[10]ELENA P,PIETRO G,ANGELO L,et al.Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer[J].Nat Med,2012,18(5):807-815.
[11]GHOBADI A.Chimeric antigen receptor T cell therapy for nonHodgkin lymphoma[J].Curr Res Translat Med,2018,66(2):43-49.
[12]LIU Y,CHEN X,HAN W,et al.Tisagenlecleucel,an approved anti-CD19 chimeric antigen receptor T-cell therapy for the treatment of leukemia[J].Drugs Today(Barcelona,Spain:1998),2017,53(11):597-608.
[13]JENSEN M C,RIDDELL S R.Design and implementation of adoptive therapy with chimeric antigen receptor-modified Tcells[J].Immunol Rev,2013,257(1):127-144.
[14]CARMINE C,MILONE M C,RAFFIT H,et al.Control of large,established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains[J].Proc Ntl Acad Sci USA,2009,106(9):3360-3365.
[15]MARKUS C,CAROLINE K,HOMBACH A A,et al.IL-12release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression[J].Cancer Res,2011,71(17):5697.
[16]ZHAO Z G,CONDOMINES M,SADELAIN M,et al.Structural design of engi-neered costimulation determines tumor rejection kinetics and persistence of CAR T cells[J].Cancer Cell,2015,28(4):415-428.
[17]BEAR A S,MORGAN R A,CORNETTA K,et al.Replication-competent retroviruses in gene-modified T cells used in clinical trials:is it time to revise the testing requirements[J].Mol Ther J Am Soci Gene Ther,2012,20(2):246.
[18]Products CfPM.Editor note for guidance on the quality,preclinical and clinical aspects of gene transfer medicinal products[S].London:The European Agency for the Evaluation of Medicinal Products,2001.
[19]CHEN J,REEVES L,CORNETTA K.Safety testing for replication-competent retrovirus associated with gibbon ape leukemia virus-pseudotyped retroviral vectors[J].Hum Gene Ther,2001,12(1):61-70.
[20]Administration UFaD.Guidance for industry:supplemental guidance on testing for replication competent retrovirus in retroviral vector based gene therapy products and during follow-up of patients in clinical trials using retroviral vectors[OL].(2001-11-14)[2018-11-17].http://www.fda.gov/Biologics-BloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Cellulara.
[21]STEPHANIE P,CHAMSY S,MARTINE B,et al.Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo[J].Proc Natl Acad Sci USA,2006,103(47):17684-17689.
[22]KATARZYNA K,SAYANDIP M,LUIS A,et al.Nonintegrating lentivector vaccines stimulate prolonged T-cell and antibody responses and are effective in tumor therapy[J].J Virol,2009,83(7):3094.
[23]CORNU T I,CATHOMEN T.Targeted genome modifications using integrase-deficient lentiviral vectors[J].Mol Ther,2007,15(12):2107-2113.
[24]GRANDCHAMP N,ALTEMIR D,PHILIPPE S,et al.Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage[J].PloS One,2014,9(6):e99649.