Advances of human papillomavirus therapeutic vaccine

Abstract

Abstract:Human papillomavirus continuous （HPV） infection is an essential factor to induce cervical intraepithelial neoplasia and cervical cancer. Treating HPV infection is considered as a starting point to develop an effective therapeutic vaccine, which is a new strategy for prevention and treatment of cervical cancer. In recent years, development and trials of therapeutic HPV vaccine have made great progress. Selection of vectors, utilization of adjuvants, synthesis of fusion proteins and chimeric proteins have been widely applied to research to enhance vaccine immunogenicity, to increase vaccination safety, to reduce the side effect and so on. The clinical trial results are encouraging: various types of vaccines can induce a specific immune response with good tolerance. However, numerous studies are still required to obtain further success. In addition, HPV exists in various forms, thus it is also the focus of study to expand the range of action and reduce immune escape.

Key words:Papillomavirus vaccine,Uterine cervical neoplasms

Wang Yinghai, Zhang Hongping, Yu Jing, Li Chunlin, Lu Yihan. Advances of human papillomavirus therapeutic vaccine[J]. Journal of International Oncology, 2017, 44(7): 526-530.

References

［1］ Wright JD, Chen L, Tergas AI, et al. Populationlevel trends in relative survival for cervical cancer［J］. Am J Obstet Gynecol, 2015, 213(5): 670, e1-7. DOI: 10.1016/j.ajog.2015.07.012. ［2］ Paunovic V, Konevic S, Paunovic T. Association of human papillomavirus infection with cytology, colposcopy, histopathology, and risk factors in the development of low and highgrade lesions of the cervix［J］. J BUON, 2016, 21(3): 659-665. ［3］ Diorio GJ, Giuliano AR. The role of human papilloma virus in penile carcinogenesis and preneoplastic lesions: a potential target for vaccination and treatment strategies［J］. Urol Clin North Am, 2016, 43(4): 419-425. DOI: 10.1016/j.ucl.2016.06.003. ［4］ Fan X, Liu Y, Heilman SA, et al. Human papillomavirus E7 induces rereplication in response to DNA damage［J］. J Virol, 2013, 87(2): 1200-1210. DOI: 10.1128/JVI.0203812. ［5］ Graham SV. Human papillomavirus E2 protein: linking replication, transcription, and RNA processing［J］. J Virol, 2016, 90(19): 8384-8388. DOI: 10.1128/JVI.0050216. ［6］ Wardak S. Human papillomavirus (HPV) and cervical cancer［J］. Med Dosw Mikrobiol, 2016, 68(1): 73-84. ［7］ Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age［J］. Nature, 2011, 480(7378): 480-489. DOI: 10.1038/nature10673. ［8］ Chen Z, Jing Y, Wen Q, et al. L1 and L2 gene polymorphisms in HPV58 and HPV33: implications for vaccine design and diagnosis［J］. Virol J, 2016, 13(1): 167. DOI: 10.1186/s1298501606299. ［9］ Herrero R, González P, Markowitz LE. Present status of human papillomavirus vaccine development and implementation［J］. Lancet Oncol, 2015, 16(5): e206-216. DOI: 10.1016/S14702045(14)704814. ［10］ Shahabi V, Maciag PC, Rivera S, et al. Live, attenuated strains of Listeria and Salmonella as vaccine vectors in cancer treatment［J］. Bioeng Bugs, 2010, 1(4): 235-243. DOI: 10.4161/bbug.1.4.11243. ［11］ Maciag PC, Radulovic S, Rothman J. The first clinical use of a liveattenuated Listeria monocytogenes vaccine: a phase Ⅰ safety study of LmLLOE7 in patients with advanced carcinoma of the cervix［J］. Vaccine, 2009, 27(30): 3975-3983. DOI: 10.1016/j.vaccine.2009.04.041. ［12］ Cory L, Chu C. ADXSHPV: a therapeutic Listeria vaccination targeting cervical cancers expressing the HPV E7 antigen［J］. Hum Vaccin Immunother, 2014, 10(11): 3190-3195. DOI: 10.4161/hv.34378. ［13］ Petit RG, Mehta A, Jain M, et al. ADXS11001 immunotherapy targeting HPVE7: final results from a phase Ⅱ study in Indian women with recurrent cervical cancer［J］. J Immuno Thera Cancer, 2014, 2 Suppl 3: P92. DOI: 10.1186/2051-1426-2-S3-P92. ［14］ Sun YY, Peng S, Han L, et al. Local HPV recombinant vaccinia boost following priming with an HPV DNA vaccine enhances local HPVspecific CD8+ Tcellmediated tumor control in the genital tract［J］. Clin Cancer Res, 2016, 22(3): 657-669. DOI: 10.1158/1078-0432.CCR-15-0234. ［15］ Lee SY, Kang TH, Knoff J, et al. Intratumoral injection of therapeutic HPV vaccinia vaccine following cisplatin enhances HPVspecific antitumor effects［J］. Cancer Immunol Immunother, 2013, 62(7): 11751185. DOI: 10.1007/s002620131421y. ［16］ 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. ［17］ Brun JL, Dalstein V, Leveque J, et al. Regression of highgrade cervical intraepithelial neoplasia with TG4001 targeted immunotherapy［J］. Am J Obstet Gynecol, 2011, 204(2): 169， e1-8. DOI: 10.1016/j.ajog.2010.09.020. ［18］ Xiao J, Zhou J, Fu M, et al. Efficacy of recombinant human adenovirusp53 combined with chemotherapy for locally advanced cervical cancer: a clinical trial［J］. Oncology Letters, 2017, 13: 3676-3680. DOI: 10.3892/ol.2017.5901. ［19］ Yang B, Jeang J, Yang A, et al. DNA vaccine for cancer immunotherapy［J］. Hum Vaccin Immunother, 2014, 10(11): 3153-3164. DOI: 10.4161/21645515.2014.980686. ［20］ 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. ［21］ Maldonado L, Teague JE, Morrow MP, et al. Intramuscular therapeutic vaccination targeting HPV16 induces T cell responses that localize in mucosal lesions［J］. Sci Transl Med, 2014, 6(221): 221ra13. DOI: 10.1126/scitranslmed.3007323. ［22］ 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): 2078-2788. DOI: 10.1016/S01406736(15)002391. ［23］ Melief CJ. Treatment of established lesions caused by highrisk human papilloma virus using a synthetic vaccine［J］. J Immunother, 2012, 35(3): 215-216. DOI: 10.1097/CJI.0b013e318248f17f. ［24］ van Poelgeest MI, Welters MJ, van Esch EM, et al. HPV16 synthetic long peptide (HPV16SLP) vaccination therapy of patients with advanced or recurrent HPV16 induced gynecological carcinoma, a phase Ⅱ trial［J］. J Transl Med, 2013, 11: 88. DOI: 10.1186/1479-5876-11-88. ［25］ Hellner K, Münger K. Human papillomaviruses as therapeutic targets in human cancer［J］. J Clin Oncol, 2011, 29(13): 1785-1794. DOI: 10.1200/JCO.2010.28.2186. ［26］ Van Doorslaer K, Reimers LL, Studentsov YY, et al. Serological response to an HPV16 E7 based therapeutic vaccine in women with highgrade cervical dysplasia［J］. Gynecol Oncol, 2010, 116(2): 208-212. DOI: 10.1016/j.ygyno.2009.05.044. ［27］ Nurkkala M, Wassén L, Nordstrm I, et al. Conjugation of HPV16 E7 to cholera toxin enhances the HPVspecific Tcell recall responses to pulsed dendritic cells in vitro in women with cervical dysplasia［J］. Vaccine, 2010, 28(36): 5828-5836. DOI: 10.1016/j.vaccine.2010.06.068. ［28］ Wang YT, Li W, Liu Q, et al. Dendritic cells treated with HPV16mE7 in a threedimensional model promote the secretion of IL12p70 and INF-γ［J］. Exp Mol Pathol, 2011, 91(1): 325-330. DOI: 10.1016/j.yexmp.2011.03.005. ［29］ Hu YX, Li M, Jia XH, et al. HPV16 CTL epitope peptideactivated dendritic cell and natural killer coculture for therapy of cervical cancer in an animal model［J］. Asian Pac J Cancer Prev, 2013, 14(12): 7335-7338. ［30］ Liu Z, Zhou H, Wang W, et al. A novel dendritic cell targeting HPV16 E7 synthetic vaccine in combination with PDL1 blockade elicits therapeutic antitumor immunity in mice［J］. Oncoimmunology, 2016, 5(6): e1147641. DOI: 10.1080/2162402X.2016.1147641. ［31］ Wu XM, Liu X, Jiao QF, et al. Cytotoxic T lymphocytes elicited by dendritic celltargeted delivery of human papillomavirus type16 E6/E7 fusion gene exert lethal effects on CaSki cells［J］. Asian Pac J Cancer Prev, 2014, 15(6): 2447-2451. ［32］ Ramanathan P, Ganeshrajah S, Raghanvan RK, et al. Development and clinical evaluation of dendritic cell vaccines for HPV related cervical cancer—a feasibility study［J］. Asian Pac J Cancer Prev, 2014, 15(14): 5909-5916. ［33］ Chen B, Liu L, Xu H, et al. Effectiveness of immune therapy combined with chemotherapy on the immune function and recurrence rate of cervical cancer［J］. Exp Ther Med, 2015, 9(3): 1063-1067. DOI: 10.3892/etm.2015.2217.

[1]	Zhang Ningning, Yang Zhe, Tan Limei, Li Zhenning, Wang Di, Wei Yongzhi.Diagnostic value of cervical cell DNA ploidy analysis combined with B7-H4 and PKCδ for cervical cancer[J]. Journal of International Oncology, 2024, 51(5): 286-291.
[2]	Zhang Lu, Jiang Hua, Lin Zhou, Ma Chenying, Xu Xiaoting, Wang Lili, Zhou Juying.Analysis of curative effect and prognosis of immune checkpoint inhibitor in the treatment of recurrent and metastatic cervical cancer[J]. Journal of International Oncology, 2023, 50(8): 475-483.
[3]	Lyu Lu, Sun Pengfei.Gut flora and cervical cancer[J]. Journal of International Oncology, 2023, 50(6): 373-376.
[4]	Ma Xueyan, Lu Lili, Sun Pengfei.Advances in the immune microenvironment in cervical cancer[J]. Journal of International Oncology, 2023, 50(1): 47-50.
[5]	Zhang Lu, Zhou Juying, Ma Chenying, Lin Zhou.Advances in immunotherapy for recurrent and metastatic cervical cancer[J]. Journal of International Oncology, 2022, 49(9): 517-520.
[6]	Shi Yingxia, Hu Lijun, Yu Jingping.Application of immune checkpoint inhibitors in the treatment of recurrent or metastatic cervical cancer[J]. Journal of International Oncology, 2022, 49(9): 568-571.
[7]	Peng Chen, Xie Yintong, Zhang Xin, Xie Peng.Research progress of maintenance therapy for cervical cancer[J]. Journal of International Oncology, 2022, 49(7): 430-435.
[8]	Yuan Chenyang, Zhou Juying.Research progress on prognostic factors of cervical cancer[J]. Journal of International Oncology, 2022, 49(5): 307-313.
[9]	Wang Yue, Wu Qiong, Xu Yuan, Gong Wei, Xu Xiaoting.Screening and treatment progression of elderly cervical cancer[J]. Journal of International Oncology, 2022, 49(12): 754-758.
[10]	Ma Xiuzhen, Lu Yan, Zhao Bingbing, Qiu Hongcong, Xu Xun, Wei Min.Effects of total flavonoids from Baeckea frutescens on the migration, invasion and apoptosis of cervical cancer SiHa cells[J]. Journal of International Oncology, 2021, 48(4): 206-211.
[11]	Yu Mingyue, Chen Zhengzheng, Zhao Xuxu, Ren Pingping, Zhang Ying, Ge Li, Zhu Meiling, Zhao Weidong.Factors related to postoperative adjuvant therapy of locally advanced cervical cancer and building of a nomogram prediction model[J]. Journal of International Oncology, 2021, 48(1): 35-40.
[12]	Ding Xuchao, Cao Lili.Common active targeting nano drug delivery systems for cervical cancer[J]. Journal of International Oncology, 2021, 48(1): 61-64.
[13]	Shu Hang, Xu Zhonghua, Zhu Haochen, Yang Yahui, Lyu Yin.Research progress of radiosensitivity in cervical cancer[J]. Journal of International Oncology, 2020, 47(8): 496-500.
[14]	Zheng Xin, Chen Xiaopin.Relationship between HPV and oropharyngeal cancer in China[J]. Journal of International Oncology, 2020, 47(3): 164-168.
[15]	Song Mingze, Cheng Yiming, Li Gang, Wang Zhenming, Li Shirong.Value of P16/Ki-67 double staining detection in screening cervical cancer and precancerous lesions[J]. Journal of International Oncology, 2020, 47(11): 675-681.