N-terminally fusion of Her2/neu to HSP70 decreases efficiency of Her2/neu DNA vaccine

Cell Stress and Chaperones - Tập 15 - Trang 631-638 - 2010
Nafiseh Pakravan1, Sara Soudi1, Zuhair Mohammad Hassan1
1Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Tóm tắt

DNA vaccines consisted of tumor-associated antigen (TAA) are well suited for immunotherapy against tumor. The construct can contain TAA fused to an appropriate molecule (biologic adjuvant) to improve the efficacy of anti-tumor immune response. Heat shock protein 70 (HSP70) has been shown to be an excellent candidate, capable of cross-priming TAA by antigen presenting cells leading to a robust T-cell response. However, the relationship between strong T-cell responses and tumor rejection is not always mutually exclusive, for which TAA loss or activation of suppressive mechanisms may occur. HSP70 fused to downstream of Her2/neu as DNA vaccine has been shown to be efficient against Her2-expressing tumors. In this study, we examined if N-terminally fusion of Her2/neu to HSP70 could also improve efficiency of Her2/neu DNA vaccine. Therefore, mice with an established Her2/neu expressing tumor were immunized with DNA vaccine consisting of extracellular and trans-membrane domain (EC+TM) of rat Her2/neu alone or N-terminally fused to HSP70 and immune response was evaluated. Administration of rat Her2/neu led to partial control of tumor progression. Surprisingly, fusion of HSP70 to N-terminal of rat Her2/neu led to tumor progression. Our result proposes that fusion direction of biologic adjuvant is an important consideration when Her2/neu is used.

Tài liệu tham khảo

Amici A, Venanzi FM, Concetti A (1998) Genetic immunization against neu/erbB2 transgenic breast cancer. Cancer Immunol Immunother 47:183–190 Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T et al (2004) PD-L1/B7-H1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD81 T cells. Cancer Res 64:1140–1145 Baxevanis CN, Sotiropoulou PA, Sotiriadou NN, Papamichail M (2004) Immunobiology of HER-2/neu oncoprotein and its potential application in cancer immunotherapy. Cancer Immunol Immunother 53(3):166–175 Boyle JS, Brady JL, Koniaras C, Lew AM (1998) Inhibitory effect of lipopolysaccharide on immune response after DNA immunization is route dependent. DNA Cell Biol 17(4):343–348 Castelli C, Rivoltini L, Rini F, Belli F, Testori A, Maio M et al (2004) Heat shock proteins: biological functions and clinical application as personalized vaccines for human cancer. Cancer Immunol Immunother 53:227–233 Chakraborty NG, Li L, Sporn JR, Kurtzman SH, Ergin MT, Mukherji B (1999) Emergence of regulatory CD4+ T cell response to repetitive stimulation with antigen-presenting cells in vitro: implications in designing antigen-presenting cell-based tumor vaccines. J Immunol 162:5576–5583 Chen CH, Wang TL, Hung CF, Yang Y, Young RA, Pardoll DM et al (2000) Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene. Cancer Res 60(4):1035–1042 Curcio C, Di Carlo E, Clynes R, Smyth MJ, Boggio K, Quaglino E et al (2003) Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas. J Clin Invest 111:1161–1170 Curier TJ, Coukos G, Zou LH, Alvarez X, Cheng P, Mottram P et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters privilege and predicts reduced survival. Nat Med 10:942–949 Geng H, Zhang GM, Xiao H, Yuan Y, Li D, Zhang H et al (2006) HSP70 vaccine in combination with gene therapy with plasmid DNA encoding sPD-1 overcomes immune resistance and suppresses the progression of pulmonary metastatic melanoma. Int J Cancer 118(11):2657–2664 Gordon NF, Clark BL (2004) The challenges of bringing autologous HSP-based vaccines to commercial reality. Methods 32:63–69 Hashemi SM, Hassan ZM, Soudi S, Ghazanfari T, Kheirandish M, Shahabi S (2007) Evaluation of anti-tumor effects of tumor cell lysate enriched by HSP-70 against fibrosarcoma tumor in BALB/c mice. Int Immunopharmacol 7(7):920–927 He YF, Wang XH, Zhang GM, Chen HT, Zhang H, Feng ZH (2005) Sustained low-level expression of interferon-g promotes tumor development: potential insights in tumor prevention and tumor immunotherapy. Cancer Immunol Immunother 54:891–897 Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M et al (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 65:1089–1096 Hsu KF, Hung CF, Cheng WF, He L, Slater LA, Ling M et al (2001) Enhancement of suicidal DNA vaccine potency by linking Mycobacterium tuberculosis heat shock protein 70 to an antigen. Gene Ther 8(5):376–383 Jiang H, Chess L (2009) How the immune system achieves self-nonself discrimination during adaptive immunity. Adv Immunol 102:95–133 Kim JH, Majumder N, Lin H, Chen J, Falo LD Jr, You Z (2005) Enhanced immunity by NeuEDhsp70 DNA vaccine is needed to combat an aggressive spontaneous metastatic breast cancer. Mol Ther 11(6):941–949 Kmieciak M, Knutson KL, Dumur CI, Manjili MH (2007) HER-2/neu antigen loss and relapse of mammary carcinoma are actively induced by T cell-mediated anti-tumor immune responses. Eur J Immunol 37(3):675–685 Kominsky SL, Hobeika AC, Lake FA, Torres BA, Johnson HM (2000a) Down-regulation of neu/HER-2 by interferon-γ in prostate cancer cells. Cancer Res 60(14):3904–3908 Kominsky SL, Hobeika AC, Lake FA, Torres BA, Johnson HM (2000b) Down-regulation of neu/HER-2 by interferon-γ in prostate cancer cells. Cancer Res 60:3904–3908 Lan YH, Li YG, Liang ZW, Chen M, Peng ML, Tang L et al (2007) A DNA vaccine against chimeric AFP enhanced by HSP70 suppresses growth of hepatocellular carcinoma. Cancer Immunol Immunother 56(7):1009–1016 Lepique AP, Regina K, Daghastanli P, Cuccovia IM, Villa LL (2009) HPV16 tumor associated macrophages suppress antitumor T cell responses. Clin Cancer Res 15(13):4391–4400 Li Y, Subjeck J, Yang G, Repasky E, Wang XY (2006) Generation of anti-tumor immunity using mammalian heat shock protein 70 DNA vaccines for cancer immunotherapy. Vaccine 24(25):5360–5370 Li H, Ou X, Xiong J (2007) Modified HPV16 E7/HSP70 DNA vaccine with high safety and enhanced cellular immunity represses murine lung metastatic tumors with downregulated expression of MHC class I molecules. Gynecol Oncol 104(3):564–571 Lin CC, Chou CW, Shiau AL, Tu CF, Ko TM, Chen YL et al (2004) Therapeutic HER2/Neu DNA vaccine inhibits mouse tumor naturally over expressing endogenous neu. Mol Ther 10(2):290–301 Lindquist S (1985) The heat-shock response. Ann Rev Biochem 55:1151–1191 Liso A, Benedetti R, Fagioli M, Mariano A, Falini B (2005) Modulatory effects of mycobacterial heat-shock protein 70 in DNA vaccination against lymphoma. Haematologica 90(1):60–65 Ma JH, Sui YF, Ye J, Huang YY, Li ZS, Chen GS et al (2005) Heat shock protein 70/MAGE-3 fusion protein vaccine can enhance cellular and humoral immune responses to MAGE-3 in vivo. Cancer Immunol Immunother 54(9):907–914 Nagata Y, Furugen R, Hiasa A, Ikeda H, Ohta N, Furukawa K et al (1997) Peptides derived from a wild-type murine protooncogene c-erbB-2/HER2/2 neu can induce CTL and tumor suppression in syngeneic hosts. J Immunol 159:1336–1343 Pavlenko M, Roos AK, Leder C, Hansson LO, Kiessling R, Levitskaya E et al (2004) Comparison of PSA-specific CD8+ CTL responses and antitumor immunity generated by plasmid DNA vaccines encoding PSA-HSP chimeric proteins. Cancer Immunol Immunother 53(12):1085–1092 Piechocki MP, Pilon SA, Wei WZ (2001) Complementary antitumor immunity induced by plasmid DNA encoding secreted and cytoplasmic human erbb-2. J Immunol 167:3367–3374 Quaglino E, Mastini C, Iezzi M, ForniG MP, Klapper LN et al (2005) The adjuvant activity of BAT antibody enables DNA vaccination to inhibit the progression of established autochthonous Her-2/neu carcinomas in BALB/c mice. Vaccine 23(25):3280–3287 Rolla S, Marchini C, Malinarich S, Quaglino E, Lanzardo S, Montani M et al (2008) Protective immunity against neu-positive carcinomas elicited by electroporation of plasmids encoding decreasing fragments of rat neu extracellular domain. Hum Gene Ther 19(3):229–240 Rovero S, Amici A, Carlo ED, Bei R, Nanni P, Quaglino E et al (2000) DNA vaccination against rat Her-2/neu p185 more effectively inhibits carcinogenesis than transplantable carcinomas in transgenic BALB/c mice. J Immunol 165(9):5133–5142 Sambrook J, Russell DW (2001) Molecular cloning: a laboratory manual, 3rd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 1.38–1.41, & 1.59–1.61 Schuler T, Qin Z, Ibe S, Noben-Trauth N, Blankenstein T (1999) T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice. J Exp Med 189:803–810 Shevach EM (2006) From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 25:195–201 Spoelstra FM, Postma DS, Hovenga H, Noordhoek JA, Kauffman HF (1999) Interferon-gamma and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung fibroblasts. Eur Respir J 14:759–766 Srivastava P (2002) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20:395–425 Thornhill MH, Wellicome SM, Mahiouz DL, Lanchbury JS, Kyan-Aung U, Haskard DO (1991) Tumor necrosis factor combines with IL-4 or IFN-gamma to selectively enhance endothelial cell adhesiveness for T cells. The contribution of vascular cell adhesion molecule-1-dependent and -independent binding. J Immunol 146(2):592–598 Udono H, Srivastava PK (1993) Heat-shock protein-70 associated peptides elicit specific cancer immunity. J Exp Med 178:1391–1396 Wang XY, Kazim L, Repasky EA, Subjeck JR (2001) Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccine activity. J Immunol 166:490–497 Wang XP, Liu GZ, Song AL, Li HY, Liu Y (2004) Antitumor immunity induced by DNA vaccine encoding alpha-fetoprotein/heat shock protein 70. World J Gastroenterol 10(21):3197–3200 Wei WZ, Shi WP, Galy A, Lichlyter D, Hernandez S, Groner B et al (1999) Protection against mammary tumor growth by vaccination with full-length, modified human ErbB-2 DNA. Int J Cancer 81(5):748–754 Worschech A, Kmieciak M, Knutson KL, Bear HD, Szalay AA, Wang E et al (2008) Signatures associated with rejection or recurrence in HER-2/neu-positive mammary tumors. Cancer Res 68(7):2436–2446 Ye J, Chen GS, Song HP, Li ZS, Huang YY, Qu P, Sun YJ, Zhang XM, Sui YF (2004) Heat shock protein 70 / MAGE-1 tumor vaccine can enhance the potency of MAGE-1-specific cellular immune responses in vivo. Cancer Immunol Immunother 53(9):825–834 Yoshino I, Peoples GE, Goedegebuure PS, Maziarz R, Eberlein TJ (1994) Association of HER2/neu expression with sensitivity to tumor-specific CTL in human ovarian cancer. J Immunol 152(5):2393–2400 Zhang H, Huang W (2006) Fusion proteins of Hsp70 with tumor-associated antigen acting as a potent tumor vaccine and the C-terminal peptide-binding domain of Hsp70 being essential in inducing antigen-independent anti-tumor response in vivo. Cell Stress Chaperones 11(3):216–226 Zhang X, Yu C, Zhao J, Fu L, Yi S, Liu S et al (2007) Vaccination with a DNA vaccine based on human PSCA and HSP70 adjuvant enhances the antigen-specific CD8+ T-cell response and inhibits the PSCA+ tumors growth in mice. J Gene Med 9(8):715–726