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Mannan-modified adenovirus encoding VEGFR-2 as a vaccine to induce anti-tumor immunity

  • Original Paper
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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Dendritic cell (DC) vaccines are a promising immunotherapeutic approach for treatment and prevention of cancer. While this methodology is widely accepted, it also has some limitations. Antigen-presenting cells including DCs express the mannan receptor (MR). The delivery of a mannan-modified tumor antigen to the MR has been demonstrated to be efficient. Vascular endothelial growth factor receptor-2 (VEGFR-2) is mainly responsible for angiogenesis and tumor growth. The goal of our study was to deliver VEGFR-2 to DCs by means of mannan-modified adenovirus.

Methods

VEGFR-2 recombinant adenovirus modified with oxidized mannan was constructed as a tumor vaccine to immunize mice in vivo. IFN-γ in mouse sera and spleen was detected by ELISA and ELISPOT. The killing activity of cytotoxic T lymphocyte (CTL) against VEGFR-2 was measured with a lactate dehydrogenase assay. Vessel densities in tumor tissues were detected by immunohistochemistry. Flow cytometry was used to test CD4+ and CD8+ T-cell counts in tumor tissues.

Results

The vaccine exhibited both protective and therapeutic efficacy in the inhibition of tumor growth and markedly prolonged survival in mice. Protection against metastasis was also observed. Furthermore, vaccination led to greater IFN-γ and VEGFR-2-specific CTLs. The specific immunity resulted in the suppression of angiogenesis and an increase in CD8+ cells in tumor tissues.

Conclusion

Oxidized mannan-modified adenovirus expressing VEGFR-2 could extraordinarily stimulate both protective and therapeutic immune response in a mice model. Our data suggest that the combination of cancer immunity and anti-angiogenesis via modified mannan is a promising strategy in tumor prophylaxis and therapy.

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References

  • Apostolopoulos V, Pietersz GA, Loveland BE, Sandrin MS, McKenzie IF (1995) Oxidative/reductive conjugation of mannan to antigen selects for T1 or T2 immune responses. Proc Natl Acad Sci USA 92(22):10128–10132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Azadmehr A, Pourfathollah AA, Amirghofran Z, Hassan ZM, Moazzeni SM (2013) Immunotherapy with tumor cell lysate-pulsed CD8 alpha + dendritic cells modulates intra-tumor and spleen lymphocyte subpopulations. Neoplasma 60(5):525–532. doi:10.4149/neo_2013_068

    Article  CAS  PubMed  Google Scholar 

  • Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5(4):296–306. doi:10.1038/nri1592

    Article  CAS  PubMed  Google Scholar 

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252. doi:10.1038/32588

    Article  CAS  PubMed  Google Scholar 

  • Bequet-Romero M, Ayala M, Acevedo BE, Rodriguez EG, Ocejo OL, Torrens I, Gavilondo JV (2007) Prophylactic naked DNA vaccination with the human vascular endothelial growth factor induces an anti-tumor response in C57Bl/6 mice. Angiogenesis 10(1):23–34. doi:10.1007/s10456-006-9062-9

    Article  CAS  PubMed  Google Scholar 

  • Blankenstein T, Coulie PG, Gilboa E, Jaffee EM (2012) The determinants of tumour immunogenicity. Nat Rev Cancer 12(4):307–313. doi:10.1038/nrc3246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cherif MS, Shuaibu MN, Kurosaki T, Helegbe GK, Kikuchi M, Yanagi T, Tsuboi T, Sasaki H, Hirayama K (2011) Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration. Vaccine 29(48):9038–9050. doi:10.1016/j.vaccine.2011.09.031

    Article  CAS  PubMed  Google Scholar 

  • Chia WK, Wang WW, Teo M, Tai WM, Lim WT, Tan EH, Leong SS, Sun L, Chen JJ, Gottschalk S, Toh HC (2012) A phase II study evaluating the safety and efficacy of an adenovirus-DeltaLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma. Ann Oncol 23(4):997–1005. doi:10.1093/annonc/mdr341

    Article  CAS  PubMed  Google Scholar 

  • Danylesko I, Beider K, Shimoni A, Nagler A (2012) Novel strategies for immunotherapy in multiple myeloma: previous experience and future directions. Clin Dev Immunol 2012:753407. doi:10.1155/2012/753407

    Article  PubMed  PubMed Central  Google Scholar 

  • Decker T, Lohmann-Matthes ML (1988) A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 115(1):61–69

    Article  CAS  PubMed  Google Scholar 

  • Ding ZY, Wu Y, Luo Y, Su JM, Li Q, Zhang XW, Liu JY, He QM, Yang L, Tian L, Zhao X, Deng HX, Wen YJ, Li J, Kang B, Wei YQ (2007) Mannan-modified adenovirus as a vaccine to induce antitumor immunity. Gene Ther 14(8):657–663. doi:10.1038/sj.gt.3302893

    Article  CAS  PubMed  Google Scholar 

  • Dong J, Yang J, Chen MQ, Wang XC, Wu ZP, Chen Y, Wang ZQ, Li M (2008) A comparative study of gene vaccines encoding different extracellular domains of the vascular endothelial growth factor receptor 2 in the mouse model of colon adenocarcinoma CT-26. Cancer Biol Ther 7(4):502–509

    Article  CAS  PubMed  Google Scholar 

  • Drake CG, Jaffee E, Pardoll DM (2006) Mechanisms of immune evasion by tumors. Adv Immunol 90:51–81

    Article  CAS  PubMed  Google Scholar 

  • Du C, Wang Y (2011) The immunoregulatory mechanisms of carcinoma for its survival and development. J Exp Clin Cancer Res 30:12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • East L, Isacke CM (2002) The mannose receptor family. Biochim Biophys Acta 1572(2–3):364–386

    Article  CAS  PubMed  Google Scholar 

  • Eggert AA, Schreurs MW, Boerman OC, Oyen WJ, de Boer AJ, Punt CJ, Figdor CG, Adema GJ (1999) Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res 59(14):3340–3345

    CAS  PubMed  Google Scholar 

  • Eggert AO, Becker JC, Ammon M, McLellan AD, Renner G, Merkel A, Brocker EB, Kampgen E (2002) Specific peptide-mediated immunity against established melanoma tumors with dendritic cells requires IL-2 and fetal calf serum-free cell culture. Eur J Immunol 32(1):122–127. doi:10.1002/1521-4141(200201)32:1<122::AID-IMMU122>3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  • Gabrilovich DI, Ishida T, Nadaf S, Ohm JE, Carbone DP (1999) Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin Cancer Res 5(10):2963–2970

    CAS  PubMed  Google Scholar 

  • Gaengel K, Niaudet C, Hagikura K, Lavina B, Muhl L, Hofmann JJ, Ebarasi L, Nystrom S, Rymo S, Chen LL, Pang MF, Jin Y, Raschperger E, Roswall P, Schulte D, Benedito R, Larsson J, Hellstrom M, Fuxe J, Uhlen P, Adams R, Jakobsson L, Majumdar A, Vestweber D, Uv A, Betsholtz C (2012) The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev Cell 23(3):587–599. doi:10.1016/j.devcel.2012.08.005

    Article  CAS  PubMed  Google Scholar 

  • Gajewski TF, Woo SR, Zha Y, Spaapen R, Zheng Y, Corrales L, Spranger S (2013) Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol 25(2):268–276. doi:10.1016/j.coi.2013.02.009

    Article  CAS  PubMed  Google Scholar 

  • Gille H, Kowalski J, Li B, LeCouter J, Moffat B, Zioncheck TF, Pelletier N, Ferrara N (2001) Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J Biol Chem 276(5):3222–3230. doi:10.1074/jbc.M002016200M002016200

    Article  CAS  PubMed  Google Scholar 

  • Gu A, Tsark W, Holmes KV, Shively JE (2009) Role of Ceacam1 in VEGF induced vasculogenesis of murine embryonic stem cell-derived embryoid bodies in 3D culture. Exp Cell Res 315(10):1668–1682. doi:10.1016/j.yexcr.2009.02.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H (1998) The central role of CD4(+) T cells in the antitumor immune response. J Exp Med 188(12):2357–2368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ibe S, Qin Z, Schuler T, Preiss S, Blankenstein T (2001) Tumor rejection by disturbing tumor stroma cell interactions. J Exp Med 194(11):1549–1559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Irjala H, Johansson EL, Grenman R, Alanen K, Salmi M, Jalkanen S (2001) Mannose receptor is a novel ligand for l-selectin and mediates lymphocyte binding to lymphatic endothelium. J Exp Med 194(8):1033–1042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jahnisch H, Fussel S, Kiessling A, Wehner R, Zastrow S, Bachmann M, Rieber EP, Wirth MP, Schmitz M (2010) Dendritic cell-based immunotherapy for prostate cancer. Clin Dev Immunol 2010:517493. doi:10.1155/2010/517493

    Article  PubMed  PubMed Central  Google Scholar 

  • Jeon YH, Choi Y, Kim CW, Kim YH, Youn H, Lee J, Chung JK (2010) Human sodium/iodide symporter-mediated radioiodine gene therapy enhances the killing activities of CTLs in a mouse tumor model. Mol Cancer Ther 9(1):126–133. doi:10.1158/1535-7163.MCT-09-0540

    Article  CAS  PubMed  Google Scholar 

  • Joshi MD, Unger WJ, Storm G, van Kooyk Y, Mastrobattista E (2012) Targeting tumor antigens to dendritic cells using particulate carriers. J Control Release 161(1):25–37

    Article  CAS  PubMed  Google Scholar 

  • Kochenderfer JN, Gress RE (2007) A comparison and critical analysis of preclinical anticancer vaccination strategies. Exp Biol Med (Maywood) 232(9):1130–1141. doi:10.3181/0702-MR-42232/9/1130

    Article  CAS  Google Scholar 

  • Lee S, Margolin K (2012) Tumor-infiltrating lymphocytes in melanoma. Curr Oncol Rep 14(5):468–474. doi:10.1007/s11912-012-0257-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee SJ, Lim HJ, Choi YH, Chang YH, Lee WJ, Kim do W, Yoon GS (2013) The clinical significance of tumor-infiltrating lymphocytes and microscopic satellites in acral melanoma in a Korean population. Ann Dermatol 25(1):61–66. doi:10.5021/ad.2013.25.1.61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lue C, van den Wall Bake AW, Prince SJ, Julian BA, Tseng ML, Radl J, Elson CO, Mestecky J (1994) Intraperitoneal immunization of human subjects with tetanus toxoid induces specific antibody-secreting cells in the peritoneal cavity and in the circulation, but fails to elicit a secretory IgA response. Clin Exp Immunol 96(2):356–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo Y, Markowitz D, Xiang R, Zhou H, Reisfeld RA (2007) FLK-1-based minigene vaccines induce T cell-mediated suppression of angiogenesis and tumor protective immunity in syngeneic BALB/c mice. Vaccine 25(8):1409–1415

    Article  CAS  PubMed  Google Scholar 

  • Mahmoud S, Lee A, Ellis I, Green A (2012) CD8(+) T lymphocytes infiltrating breast cancer: a promising new prognostic marker? Oncoimmunology 1(3):364–365. doi:10.4161/onci.186142011ONCOIMM0086

    Article  PubMed  PubMed Central  Google Scholar 

  • Matsushita N, Aruga A, Inoue Y, Kotera Y, Takeda K, Yamamoto M (2013) Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer. Oncol Rep 29(3):951–959. doi:10.3892/or.2013.2231

    CAS  PubMed  Google Scholar 

  • Mayordomo JI, Zorina T, Storkus WJ, Zitvogel L, Garcia-Prats MD, DeLeo AB, Lotze MT (1997) Bone marrow-derived dendritic cells serve as potent adjuvants for peptide-based antitumor vaccines. Stem Cells 15(2):94–103. doi:10.1002/stem.150094

    Article  CAS  PubMed  Google Scholar 

  • McMahon G (2000) VEGF receptor signaling in tumor angiogenesis. Oncologist 5(Suppl 1):3–10

    Article  CAS  PubMed  Google Scholar 

  • Mimura K, Kono K, Takahashi A, Kawaguchi Y, Fujii H (2007) Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2. Cancer Immunol Immunother 56(6):761–770. doi:10.1007/s00262-006-0234-7

    Article  CAS  PubMed  Google Scholar 

  • Miyazawa M, Ohsawa R, Tsunoda T, Hirono S, Kawai M, Tani M, Nakamura Y, Yamaue H (2010) Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer. Cancer Sci 101(2):433–439. doi:10.1111/j.1349-7006.2009.01416.x

    Article  CAS  PubMed  Google Scholar 

  • Morera Y, Bequet-Romero M, Ayala M, Lamdan H, Agger EM, Andersen P, Gavilondo JV (2008) Anti-tumoral effect of active immunotherapy in C57BL/6 mice using a recombinant human VEGF protein as antigen and three chemically unrelated adjuvants. Angiogenesis 11(4):381–393. doi:10.1007/s10456-008-9121-5

    Article  CAS  PubMed  Google Scholar 

  • Murali-Krishna K, Altman JD, Suresh M, Sourdive DJ, Zajac AJ, Miller JD, Slansky J, Ahmed R (1998) Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8(2):177–187

    Article  CAS  PubMed  Google Scholar 

  • Nair S, Boczkowski D, Moeller B, Dewhirst M, Vieweg J, Gilboa E (2003) Synergy between tumor immunotherapy and antiangiogenic therapy. Blood 102(3):964–971. doi:10.1182/blood-2002-12-37382002-12-3738

    Article  CAS  PubMed  Google Scholar 

  • Nieminen T, Toivanen PI, Rintanen N, Heikura T, Jauhiainen S, Airenne KJ, Alitalo K, Marjomaki V, Yla-Herttuala S (2014) The impact of the receptor binding profiles of the vascular endothelial growth factors on their angiogenic features. Biochim Biophys Acta 1:454–463. doi:10.1016/j.bbagen.2013.10.005

    Article  Google Scholar 

  • Pace JL, Russell SW, Torres BA, Johnson HM, Gray PW (1983) Recombinant mouse gamma interferon induces the priming step in macrophage activation for tumor cell killing. J Immunol 130(5):2011–2013

    CAS  PubMed  Google Scholar 

  • Palucka K, Banchereau J (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12(4):265–277. doi:10.1038/nrc3258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prado-Garcia H, Romero-Garcia S, Aguilar-Cazares D, Meneses-Flores M, Lopez-Gonzalez JS (2012) Tumor-induced CD8 + T-cell dysfunction in lung cancer patients. Clin Dev Immunol 2012:741741. doi:10.1155/2012/741741

    Article  PubMed  PubMed Central  Google Scholar 

  • Prevost-Blondel A, Neuenhahn M, Rawiel M, Pircher H (2000) Differential requirement of perforin and IFN-gamma in CD8 T cell-mediated immune responses against B16.F10 melanoma cells expressing a viral antigen. Eur J Immunol 30(9):2507–2515. doi:10.1002/1521-4141(200009)30:9<2507:AID-IMMU2507>3.0.CO;2-V

    Article  CAS  PubMed  Google Scholar 

  • Qin Z, Schwartzkopff J, Pradera F, Kammertoens T, Seliger B, Pircher H, Blankenstein T (2003) A critical requirement of interferon gamma-mediated angiostasis for tumor rejection by CD8 + T cells. Cancer Res 63(14):4095–4100

    CAS  PubMed  Google Scholar 

  • Rosenberg SA, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, White DE (2003) Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen. Hum Gene Ther 14(8):709–714. doi:10.1089/104303403765255110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sauter BV, Martinet O, Zhang WJ, Mandeli J, Woo SL (2000) Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases. Proc Natl Acad Sci USA 97(9):4802–4807. doi:10.1073/pnas.090065597090065597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schreurs MW, Eggert AA, de Boer AJ, Vissers JL, van Hall T, Offringa R, Figdor CG, Adema GJ (2000) Dendritic cells break tolerance and induce protective immunity against a melanocyte differentiation antigen in an autologous melanoma model. Cancer Res 60(24):6995–7001

    CAS  PubMed  Google Scholar 

  • Schultz RM, Kleinschmidt WJ (1983) Functional identity between murine gamma interferon and macrophage activating factor. Nature 305(5931):239–240

    Article  CAS  PubMed  Google Scholar 

  • Sheng KC, Pouniotis DS, Wright MD, Tang CK, Lazoura E, Pietersz GA, Apostolopoulos V (2006) Mannan derivatives induce phenotypic and functional maturation of mouse dendritic cells. Immunology 118(3):372–383. doi:10.1111/j.1365-2567.2006.02384.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stambas J, Pietersz G, McKenzie I, Cheers C (2002) Oxidised mannan as a novel adjuvant inducing mucosal IgA production. Vaccine 20(7–8):1068–1078

    Article  CAS  PubMed  Google Scholar 

  • Steel JC, Di Pasquale G, Ramlogan CA, Patel V, Chiorini JA, Morris JC (2013) Oral vaccination with adeno-associated virus vectors expressing the Neu oncogene inhibits the growth of murine breast cancer. Mol Ther 21(3):680–687. doi:10.1038/mt.2012.260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steitz J, Bruck J, Steinbrink K, Enk A, Knop J, Tuting T (2000) Genetic immunization of mice with human tyrosinase-related protein 2: implications for the immunotherapy of melanoma. Int J Cancer 86(1):89–94. doi:10.1002/(SICI)1097-0215(20000401)86:1<89:AID-IJC14>3.0.CO;2-I

    Article  CAS  PubMed  Google Scholar 

  • Tang CK, Sheng KC, Pouniotis D, Esparon S, Son HY, Kim CW, Pietersz GA, Apostolopoulos V (2008) Oxidized and reduced mannan mediated MUC1 DNA immunization induce effective anti-tumor responses. Vaccine 26(31):3827–3834. doi:10.1016/j.vaccine.2008.05.008

    Article  CAS  PubMed  Google Scholar 

  • Toldbod HE, Agger R, Bolund L, Hokland M (2003) Potent influence of bovine serum proteins in experimental dendritic cell-based vaccination protocols. Scand J Immunol 58(1):43–50

    Article  CAS  PubMed  Google Scholar 

  • Turkeri L, Onol FF, Ozyurek M (2010) Tumor specific cytotoxicity and telomerase down-regulation in prostate cancer by autologous dendritic cells loaded with whole tumor cell antigens. Urol Oncol 28(3):290–295. doi:10.1016/j.urolonc.2009.01.029

    Article  CAS  PubMed  Google Scholar 

  • Vajkoczy P, Farhadi M, Gaumann A, Heidenreich R, Erber R, Wunder A, Tonn JC, Menger MD, Breier G (2002) Microtumor growth initiates angiogenic sprouting with simultaneous expression of VEGF, VEGF receptor-2, and angiopoietin-2. J Clin Invest 109(6):777–785. doi:10.1172/JCI14105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vestweber D (2008) VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation. Arterioscler Thromb Vasc Biol 28(2):223–232. doi:10.1161/ATVBAHA.107.158014

    Article  CAS  PubMed  Google Scholar 

  • Wada S, Tsunoda T, Baba T, Primus FJ, Kuwano H, Shibuya M, Tahara H (2005) Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res 65(11):4939–4946. doi:10.1158/0008-5472.CAN-04-375965/11/4939

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Kaumaya PT, Cohn DE (2010) Immunization with synthetic VEGF peptides in ovarian cancer. Gynecol Oncol 119(3):564–570. doi:10.1016/j.ygyno.2010.07.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei Y, Sun Y, Song C, Li H, Li Y, Zhang K, Gong J, Liu F, Liu Z, August JT, Jin B, Yang K (2012) Enhancement of DNA vaccine efficacy by targeting the xenogeneic human chorionic gonadotropin, survivin and vascular endothelial growth factor receptor 2 combined tumor antigen to the major histocompatibility complex class II pathway. J Gene Med 14(5):353–362. doi:10.1002/jgm.2624

    Article  CAS  PubMed  Google Scholar 

  • Weidmann E, Brieger J, Jahn B, Hoelzer D, Bergmann L, Mitrou PS (1995) Lactate dehydrogenase-release assay: a reliable, nonradioactive technique for analysis of cytotoxic lymphocyte-mediated lytic activity against blasts from acute myelocytic leukemia. Ann Hematol 70(3):153–158

    Article  CAS  PubMed  Google Scholar 

  • Yan J, Jia R, Song H, Liu Y, Zhang L, Zhang W, Wang Y, Zhu Y, Yu J (2009) A promising new approach of VEGFR2-based DNA vaccine for tumor immunotherapy. Immunol Lett 126(1–2):60–66. doi:10.1016/j.imlet.2009.07.013

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Sonoda KH, Hijioka K, Qiao H, Oshima Y, Ishibashi T (2009) Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization. Biochem Biophys Res Commun 381(4):471–476. doi:10.1016/j.bbrc.2009.01.178

    Article  CAS  PubMed  Google Scholar 

  • Zhao Z, Yao Y, Ding Z, Chen X, Xie K, Luo Y, Zhang J, Wu X, Xu J, Zhao J, Niu T, Liu J, Li Q, Zhang W, Wen Y, Su J, Hu B, Bu H, Wei Y, Wu Y (2011) Antitumour immunity mediated by mannan-modified adenovirus vectors expressing VE-cadherin. Vaccine 29(25):4218–4224. doi:10.1016/j.vaccine.2011.03.109

    Article  CAS  PubMed  Google Scholar 

  • Zheng X, Koropatnick J, Chen D, Velenosi T, Ling H, Zhang X, Jiang N, Navarro B, Ichim TE, Urquhart B, Min W (2013) Silencing IDO in dendritic cells: a novel approach to enhance cancer immunotherapy in a murine breast cancer model. Int J Cancer 132(4):967–977. doi:10.1002/ijc.27710

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Sciences Foundation of China (30801373 and 81172202).

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  1. Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guo-Xue Xiang, Chengdu, 610041, Sichuan, People’s Republic of China

    Jie Zhang, Ying Wang, Yang Wu, Zhen-Yu Ding, Xin-Mei Luo, Wu-Ning Zhong, Jie Liu, Xiang-Yu Xia, Guo-Hua Deng, Yao-Tiao Deng, Yu-Quan Wei & Yu Jiang

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  1. Jie Zhang
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Correspondence to Yu Jiang.

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Jie Zhang and Ying Wang contributed equally to this work.

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Zhang, J., Wang, Y., Wu, Y. et al. Mannan-modified adenovirus encoding VEGFR-2 as a vaccine to induce anti-tumor immunity. J Cancer Res Clin Oncol 140, 701–712 (2014). https://doi.org/10.1007/s00432-014-1606-6

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