中华预防医学杂志2018年5月第52卷第5期 Chin Prey Mee,May2018Vol52,No5 et al. Regression of papilloma high-grade lesions(CIN 2 and CIN avirus type 16 and 18 E7-pulsed 3)is stimulated by therapeutic vaccination with MVA E2 vaccination of stage IB or IlA cervical cance recombinant vaccine) Caneer Gene Ther, 2006. 13(6): 592-597 ,」vil,2008.824 DOE:10.1038/sjcg.7700937 8-1979.DOl:10.1128/VL02343-07 118] Rosales R, Lopez-Contreras M. Rosales C, et al. Regression of 26 Stevanovic s, Draper LM, Langhan MM, et al. Complete uman papillomavirus intraepithelial lesions is induced by regression of metastatic cervical cancer after treatment with MVA E2 therapeutic vaccine[J Hum Gene Ther, 2014, 25(12): Iman papillomavirus-targeted tumor-infiltrating T cells[J] J 1035-1049.DOl:10.1089/hum.2014.024 Clin Oncol.201533(14)1543-1550.DO:10.1200 [19 Mahdavi A Monk B. Vaccines against human papillomavirus JCO.2014.58.9093 2005,107):528-538.D0:10.1634 oncologist.101538 and cervical cancer: promises and challenges[J. Oneologis [27 Berzofsky JA, Ahlers JD, Derby MA, et al. Approaches to improve engineered vaccines for human immunodeficiency [20) Van Tine BA, Dao LD, Wu SY, et al. Human papillomavirus virus and other viruses that cause chronic infections[JI (HPV) origin-binding protein associates with mitotie spindles mmunol rev,1999,170:151-172 to enable viral DNA partitioning J]. Proc Natl Acad Sci U S A [28) Kim H, Kwon B. Sin JI Combined stimulation of IL-2 and 2004.101(12:4030-4035.DOl:10.1073/pnas.0306848101 4-1BB receptors augments the antitumor activity of E7 DNA [21 Liu R, Zhou C, Wang D, et al. Enhancement of DNA vac potency by sandwiching antigen-coding gene between vaccines by increasing Ag-specifie CTL responses[JI. PLos One,20138(12c83765.DOl:10.137 I/joumal.pone083765 dary lymphoid tissue chemokine (SiC) and IgG Fe [29 Butterfield LH Caneer vaccines[J). BMJ, 2015, 350: 1988. fragment genes[JI. Cancer Biol Ther, 2006,5(4): 427-434 [301 Mondini M. Nizar M. Tran T, et al. Synergy of Radiotherapy 22 Alvarez RD, Huh WK, Bae S, et al. A pilot study of pNGVLAa-CRT/E7(detox) for the: treatment of patients wi and a Cancer vaccine for the Treatment of hPv-associated Head and Ne HPV16+ cervical intraepithelial neoplasia 2/3(CIN2/3)JL Gynecol Cancer]. Mol Cancer Ther, 2015. 146) 1336-1345.DOl:10.1158/1535-7163.MCT-14-1015 Ond,2016402245-252.DOl:10.1016ygm2015.11.026 [23] Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, [31] Draghiciu O, Nijman HW, Hoogeboom BN, et al. Sunitinib and immunogenicity of VGX-3100, a therapeutic synthetic depletes myeloid-derived suppressor cells and synergizes with DNA vaccine targeting human papillomavirus 16 and 18 E6 er vaccine to enhance antigen-specifie immune and E7 proteins for cervical intraepithelial neoplasia 2/3:a responses and tumor eradication[J. Oncoimmunology, 2015.4 randomised, double-blind, placebo-controlled phase 2b trial 3c989764.DO:10.4161/2162402X2014989764 [. Lancet,2015,386(10008:2078-2088.DO10.1016 [321 Kaufmann AM, Stem PL, Rankin EM, et al. Safety and 124) Liu DW, Tsao YP, Hsich CH, et al. Induction of CD8 T cells expressing modified h papillomavirus(HPV-16 and by vaccination with recombinant adenovirus expressin HPV-18 E6 and E7 genes, in women with progressive cervical human papillomavirus type 16 E5 gene reduces tumor growth cancer Jl. Clin Cancer Res, 2002, 8(12): 3676-3685 IJ virol,2000.74(19:9083-9089 (收稿日期:2017-10-30) antin AD. Bellone s. Palmieri M. et al. Human (本文编辑:梁明修)· 560 · 中华预防医学杂志 2018 年5月第 52 卷第5期 Chin J Prev Med，May 2018, Vol. 52, No. 5 et al. Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine[J]. Cancer Gene Ther, 2006,13(6):592-597. DOI: 10.1038/sj.cgt.7700937. [18] Rosales R, López-Contreras M, Rosales C, et al. Regression of human papillomavirus intraepithelial lesions is induced by MVA E2 therapeutic vaccine[J]. Hum Gene Ther, 2014,25(12): 1035-1049. DOI: 10.1089/hum.2014.024. [19] Mahdavi A, Monk BJ. Vaccines against human papillomavirus and cervical cancer: promises and challenges[J]. Oncologist, 2005,10(7):528-538. DOI: 10.1634/theoncologist.10-7-528. [20] Van Tine BA, Dao LD, Wu SY, et al. Human papillomavirus (HPV) origin-binding protein associates with mitotic spindles to enable viral DNA partitioning[J]. Proc Natl Acad Sci U S A, 2004,101(12):4030-4035. DOI: 10.1073/pnas.0306848101. [21] Liu R, Zhou C, Wang D, et al. Enhancement of DNA vaccine potency by sandwiching antigen-coding gene between secondary lymphoid tissue chemokine (SLC) and IgG Fc fragment genes[J]. Cancer Biol Ther, 2006,5(4):427-434. [22] Alvarez RD, Huh WK, Bae S, et al. A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3)[J]. Gynecol Oncol, 2016,140(2):245-252. DOI: 10.1016/j.ygyno.2015.11.026. [23] Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial [J]. Lancet, 2015,386(10008):2078-2088. DOI: 10.1016/ S0140-6736(15)00239-1. [24] Liu DW, Tsao YP, Hsieh CH, et al. Induction of CD8 T cells by vaccination with recombinant adenovirus expressing human papillomavirus type 16 E5 gene reduces tumor growth [J]. J Virol, 2000,74(19):9083-9089. [25] Santin AD, Bellone S, Palmieri M, et al. Human papillomavirus type 16 and 18 E7-pulsed dendritic cell vaccination of stage IB or IIA cervical cancer patients: a phase I escalating-dose trial[J]. J Virol, 2008,82(4): 1968-1979. DOI: 10.1128/JVI.02343-07. [26] Stevanović S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells[J]. J Clin Oncol, 2015,33(14):1543-1550. DOI: 10.1200/ JCO.2014.58.9093. [27] Berzofsky JA, Ahlers JD, Derby MA, et al. Approaches to improve engineered vaccines for human immunodeficiency virus and other viruses that cause chronic infections[J]. Immunol Rev, 1999,170:151-172. [28] Kim H, Kwon B, Sin JI. Combined stimulation of IL-2 and 4-1BB receptors augments the antitumor activity of E7 DNA vaccines by increasing Ag-specific CTL responses[J]. PLoS One, 2013,8(12):e83765. DOI: 10.1371/journal.pone.0083765. [29] Butterfield LH. Cancer vaccines[J]. BMJ, 2015,350:h988. [30] Mondini M, Nizard M, Tran T, et al. Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer[J]. Mol Cancer Ther, 2015,14(6): 1336-1345. DOI: 10.1158/1535-7163.MCT-14-1015. [31] Draghiciu O, Nijman HW, Hoogeboom BN, et al. Sunitinib depletes myeloid-derived suppressor cells and synergizes with a cancer vaccine to enhance antigen-specific immune responses and tumor eradication[J]. Oncoimmunology, 2015,4 (3):e989764. DOI: 10.4161/2162402X.2014.989764. [32] Kaufmann AM, Stern PL, Rankin EM, et al. Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer[J]. Clin Cancer Res, 2002, 8(12): 3676-3685. （收稿日期：2017-10-30） （本文编辑：梁明修）