HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo

Shu-jie Liao , Dong-rui Deng , Dan Zeng , Ling Zhang , Xiao-ji Hu , Wei-na Zhang , Li Li , Xue-feng Jiang , Chang-yu Wang , Jian-feng Zhou , Shi-xuan Wang , Han-wang Zhang , Ding Ma

Current Medical Science ›› 2013, Vol. 33 ›› Issue (5) : 735 -742.

PDF
Current Medical Science ›› 2013, Vol. 33 ›› Issue (5) : 735 -742. DOI: 10.1007/s11596-013-1189-5
Article

HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo

Author information +
History +
PDF

Abstract

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

Keywords

human papillomavirus / cervical cancer / peptide vaccine / E5

Cite this article

Download citation ▾
Shu-jie Liao, Dong-rui Deng, Dan Zeng, Ling Zhang, Xiao-ji Hu, Wei-na Zhang, Li Li, Xue-feng Jiang, Chang-yu Wang, Jian-feng Zhou, Shi-xuan Wang, Han-wang Zhang, Ding Ma. HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo. Current Medical Science, 2013, 33(5): 735-742 DOI:10.1007/s11596-013-1189-5

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

WalboomersJM, JacobsMV, ManosMM, et al.. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 1999, 189(1): 12-19

[2]

BellMC, AlvarezRD. Chemoprevention and vaccines: a review of the nonsurgical options for the treatment of cervical dysplasia. Int J Gynecol Cancer, 2005, 15(1): 4-12

[3]

MahdaviA, MonkBJ. Vaccines against human papillomavirus and cervical cancer: promises and challenges. Oncologist, 2005, 10(7): 528-538

[4]

JansenKU, ShawAR. Human papillomavirus vaccines and prevention of cervical cancer. Annu Rev Med, 2004, 55(1): 319-331

[5]

SarkarAK, Tortolero-LunaG, FollenM, et al.. Inverse correlation of cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 with recurrence of cervical intraepithelial neoplasia in a cross-sectional study. Gynecol Oncol, 2005, 99(3): S251-261

[6]

JiH, ChangEY, LinKY, et al.. Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein. Int J Cancer, 1998, 78(1): 41-45

[7]

TsaiTC, ChenSL. The biochemical and biological functions of human papillomavirus type 16 E5 protein. Arch Virol, 2003, 148(8): 1445-1453

[8]

NathR, MantCA, KellB, et al.. Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts. Cancer Cell Int, 2006, 6(1): 19-27

[9]

KrawczykE, SuprynowiczFA, SudarshanSR, et al.. Membrane orientation of the human papillomavirus type 16 E5 oncoprotein. J Virol, 2010, 84(4): 1696-1703

[10]

KiviN, GrecoD, AuvinenP, et al.. Genes involved in cell adhesion, cell motility and mitogenic signaling are altered due to HPV 16 E5 protein expression. Oncogene, 2008, 27(18): 2532-2541

[11]

Pedroza-SaavedraA, LamEW, Esquivel-GuadarramaF, et al.. The human papillomavirus type 16 E5 oncoprotein synergizes with EGF-receptor signaling to enhance cell cycle progression and the down-regulation of p27(Kip1). Virology, 2010, 400(1): 44-52

[12]

StöpplerMC, StraightSW, TsaoG, et al.. The E5 gene of HPV-16 enhances keratinocyte immortalization by full-length DNA. Virology, 1996, 223(1): 251-254

[13]

GaoP, ZhengJ. High-risk HPV E5-induced cell fusion: a critical initiating event in the early stage of HPV-associated cervical cancer. Virol J, 2010, 7(1): 238-240

[14]

BoulenouarS, WeynC, Van NoppenM, et al.. Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration and invasion of trophoblastic cells. Carcinogenesis, 2010, 31(3): 473-480

[15]

LiaoSJ, DengDR, HuXJ, et al.. HPV16/18 E5, a promising candidate for cervical cancer vaccines, affects SCPs, cell proliferation and cell cycle, and forms a potential network with E6 and E7. Int J Mol Med, 2013, 31(1): 120-128

[16]

KlinmanDM, CurrieD, GurselI, et al.. Use of CpG oligodeoxynucleotides as immune adjuvants. Immunol Rev, 2004, 199(1): 201-216

[17]

Vazquez-OrtizG, CiudadCJ, PinaP, et al.. Gene identification by cDNA arrays in HPV-positive cervical cancer. Arch Med Res, 2005, 36(5): 448-458

[18]

ParkerKC, BednarekMA, ColiganJE. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol, 1994, 152(1): 163-175

[19]

RammenseeH, BachmannJ, EmmerichNP, et al.. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics, 1999, 50(3–4): 213-219

[20]

BhasinM, RaghavaGP. Analysis and prediction of affinity of TAP binding peptides using cascade SVM. Protein Sci, 2004, 13(3): 596-607

[21]

SinghH, RaghavaGP. ProPred1: prediction of promiscuous MHC Class-I binding sites. Bioinformatics, 2003, 19(8): 1009-1014

[22]

SamorskiR, GissmannL, OsenW. Codon optimized expression of HPV 16 E6 renders target cells susceptible to E6-specific CTL recognition. Immunol Lett, 2006, 107(1): 41-49

[23]

DaftarianP, MansourM, BenoitAC, et al.. Eradication of established HPV 16-expressing tumors by a single administration of a vaccine composed of a liposome-encapsulated CTL-T helper fusion peptide in a water-in-oil emulsion. Vaccine, 2006, 24(24): 5235-5244

[24]

KozakM. At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells. J Mol Biol, 1987, 196(4): 947-950

[25]

XiaoX, LiJ, SamulskiRJ. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol, 1998, 72(3): 2224-2232

[26]

XiaoX, LiJ, SamulskiRJ. Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J Virol, 1996, 70(11): 8098-8108

[27]

ChenY, XiongT, YuL, et al.. Whole-body fluorescent optical imaging based on power light emitting diode. Conf Proc IEEE Eng Med Biol Soc, 2005, 2(1): 1442-1445

[28]

KimTY, MyoungHJ, KimJH, et al.. Both E 7 and CpG-oligodeoxynucleotide are required for protective immunity against challenge with human papillomavirus 16 (E6/E7) immortalized tumor cells: involvement of CD4+ and CD8+ T cells in protection. Cancer Res, 2002, 62(24): 7234-7240

[29]

CoolsN, PonsaertsP, LenjouM, et al.. Sensitive detection of human papillomavirus type 16 E7-specific T cells by ELISPOT after multiple in vitro stimulations of CD8+ T cells with peptide-pulsed autologous dendritic cells. Mol Cancer, 2006, 5(1): 49-56

[30]

ChenYF, LinCW, TsaoYP, et al.. Cytotoxic-T-lympho-cyte human papillomavirus type 16 E5 peptide with CpG-oligodeoxynucleotide can eliminate tumor growth in C57BL/6 mice. J Virol, 2004, 78(3): 1333-1343

[31]

FrazerIH. Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol, 2004, 4(1): 46-54

[32]

ChangJL, TsaoYP, LiuDW, et al.. The expression of HPV-16 E5 protein in squamous neoplastic changes in the uterine cervix. J Biomed Sci, 2001, 8(2): 206-213

[33]

LowyDR, SchillerJT. Prophylactic human papillomavirus vaccines. J Clin Invest, 2006, 116(5): 1167-1173

[34]

PengS, TomsonTT, TrimbleC, et al.. A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects. Gene Ther, 2006, 13(3): 257-265

[35]

LiaoSJ, DengDR, ZhangWN, et al.. Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo. Oncol Rep, 2013, 29(1): 95-102

[36]

BouvardV, MatlashewskiG, GuZM, et al.. The human papillomavirus type 16 E5 gene cooperates with the E7 gene to stimulate proliferation of primary cells and increases viral gene expression. Virology, 1994, 203(1): 73-80

[37]

GaoP, ZhengJ. High-risk HPV E5-induced cell fusion: a critical initiating event in the early stage of HPV-associated cervical cancer. Virol J, 2010, 7(1): 238-240

[38]

ZwavelingS, Ferreira MotaSC, NoutaJ, et al.. Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides. J Immunol, 2002, 169(1): 350-358

[39]

NevesPC, RudersdorfRA, GallerR, et al.. CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-gamma at 5-7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses. Vaccine, 2010, 28(51): 8183-8188

[40]

KimMK, KimHS, KimSH, et al.. Human papillomavirus type 16 E5 oncoprotein as a new target for cervical cancer treatment. Biochem Pharmacol, 2010, 80(12): 1930-1935

[41]

LiK, JinX, FangY, et al.. Correlation between physical status of human papilloma virus and cervical carcinogenesis. J Huazhong Univ Sci Technol [Med Sci], 2012, 32(1): 97-102

[42]

MaufortJP, ShaiA, PitotHC, et al.. A role for HPV16 E5 in cervical carcinogenesis. Cancer Res, 2010, 70(7): 2924-2931

AI Summary AI Mindmap
PDF

123

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/