Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research
Published in: Breast Cancer Research 2/2012

Open Access 01-04-2012 | Research article

Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice

Authors: Bei Wang, Neeha Zaidi, Li-Zhen He, Li Zhang, Janelle MY Kuroiwa, Tibor Keler, Ralph M Steinman

Published in: Breast Cancer Research | Issue 2/2012

Login to get access

Abstract

Introduction

Given their relative simplicity of manufacture and ability to be injected repeatedly, vaccines in a protein format are attractive for breast and other cancers. However, soluble human epidermal growth factor receptor (HER2)/neu protein as a vaccine has not been immunogenic. When protein is directly targeted to antigen uptake receptors, such as DEC205 (DEC), efficient processing and presentation of antigen take place. The aim of this study was to determine the immunogenicity of a HER2 protein vaccine that directly targets to DEC+ dendritic cells (DCs) in a mouse breast cancer model.

Methods

We genetically engineered the HER2 extracellular domain into a monoclonal antibody specific for DEC (DEC-HER2). Mice of various genetic backgrounds were immunized with DEC-HER2 in combination with DC maturation stimuli (poly IC ± CD40 Ab). Vaccine-induced T cell immunity was determined by analyzing the ability of CD4+/CD8+ T cell to produce interferon (IFN)-gamma and proliferate upon antigen rechallenge. Sera were assessed for the presence of antigen specific antibody (Ab). For vaccine efficacy, FVB/N mice were immunized with DEC-HER2 in combination with poly IC and protection against neu-expressing mammary tumors was assessed. Protection mechanisms and tumor-specific T cell responses were also evaluated.

Results

We demonstrate that DEC-HER2 fusion mAb, but not Ctrl Ig-HER2, elicits strong, broad and multifunctional CD4+ T cell immunity, CD8+ T cell responses, and humoral immunity specific for HER2 antigen. Cross-reactivity to rat neu protein was also observed. Importantly, mice xeno-primed with DEC-HER2 were protected from a neu-expressing mammary tumor challenge. Both CD4+ and CD8+ T cells mediated the tumor protection. Robust anti-tumor T cell immunity was detected in tumor protected mice.

Conclusions

Immunization of mice with HER2 protein vaccine targeting DEC+ DCs in vivo induced high levels of T- and B-cell immunity. Non-targeted HER2 protein was poorly immunogenic for CD4+ and CD8+ T cells. This vaccination approach provided long-term survival benefit for mice challenged with neu-expressing tumor following as little as 2.7 μg of HER2 protein incorporated in the vaccine. Vaccine-induced CD4+ and CD8+ T cells were both essential for tumor protection. This immunization strategy demonstrates great potential towards the development of vaccines for breast cancer patients.
Appendix
Available only for authorised users
Literature
1.
Yarden Y, Sliwkowski MX: Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001, 2: 127-137. 10.1038/35052073.CrossRefPubMed
2.
Baselga J, Swain SM: Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009, 9: 463-475. 10.1038/nrc2656.CrossRefPubMed
3.
Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987, 235: 177-182. 10.1126/science.3798106.CrossRefPubMed
4.
Hynes NE, Stern DF: The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta. 1994, 1198: 165-184.PubMed
5.
Pupa SM, Menard S, Andreola S, Colnaghi MI: Antibody response against the c-erbB-2 oncoprotein in breast carcinoma patients. Cancer Res. 1993, 53: 5864-5866.PubMed
6.
Disis M, Calenoff E, McLaughlin G, Murphy A, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston R, Moe R, Cheever M: Existent T cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res. 1994, 54: 16-20.PubMed
7.
Ward RL, Hawkins NJ, Coomber D, Disis ML: Antibody immunity to the HER-2/neu oncogenic protein in patients with colorectal cancer. Hum Immunol. 1999, 60: 510-515. 10.1016/S0198-8859(99)00003-8.CrossRefPubMed
8.
Disis ML, Knutson KL, Schiffman K, Rinn K, McNeel DG: Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer. Breast Cancer Res Treat. 2000, 62: 245-252. 10.1023/A:1006438507898.CrossRefPubMed
9.
Bernhard H, Salazar L, Schiffman K, Smorlesi A, Schmidt B, Knutson KL, Disis ML: Vaccination against the HER-2/neu oncogenic protein. Endocr Relat Cancer. 2002, 9: 33-44. 10.1677/erc.0.0090033.CrossRefPubMed
10.
Yoshino I, Goedegebuure PS, Peoples GE, Parikh AS, DiMaio JM, Lyerly HK, Gazdar AF, Eberlein TJ: HER2/neu-derived peptides are shared antigens among human non-small cell lung cancer and ovarian cancer. Cancer Res. 1994, 54: 3387-3390.PubMed
11.
Fisk B, Blevins TL, Wharton JT, Ioannides CG: Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J Exp Med. 1995, 181: 2109-2117. 10.1084/jem.181.6.2109.CrossRefPubMed
12.
Peiper M, Goedegebuure PS, Izbicki JR, Eberlein TJ: Pancreatic cancer associated ascites-derived CTL recognize a nine-amino-acid peptide GP2 derived from HER2/neu. Anticancer Res. 1999, 19: 2471-2475.PubMed
13.
Taylor P, Gerder M, Moros Z, Feldmann M: Humoral and cellular responses raised against the human HER2 oncoprotein are cross-reactive with the homologous product of the new proto-oncogene, but do not protect rats against B104 tumors expressing mutated neu. Cancer Immunol Immunother. 1996, 42: 179-184. 10.1007/s002620050268.CrossRefPubMed
14.
Foy TM, Bannink J, Sutherland RA, McNeill PD, Moulton GG, Smith J, Cheever MA, Grabstein K: Vaccination with Her-2/neu DNA or protein subunits protects against growth of a Her-2/neu-expressing murine tumor. Vaccine. 2001, 19: 2598-2606. 10.1016/S0264-410X(00)00493-X.CrossRefPubMed
15.
Dela Cruz JS, Lau SY, Ramirez EM, De Giovanni C, Forni G, Morrison SL, Penichet ML: Protein vaccination with the HER2/neu extracellular domain plus anti-HER2/neu antibody-cytokine fusion proteins induces a protective anti-HER2/neu immune response in mice. Vaccine. 2003, 21: 1317-1326. 10.1016/S0264-410X(02)00741-7.CrossRefPubMed
16.
Dimitriadis A, Gontinou C, Baxevanis CN, Mamalaki A: The mannosylated extracellular domain of Her2/neu produced in P. pastoris induces protective antitumor immunity. BMC Cancer. 2009, 9: 386-10.1186/1471-2407-9-386.CrossRefPubMedPubMedCentral
17.
Rohrbach F, Weth R, Kursar M, Sloots A, Mittrucker H-W, Wels WS: Targeted delivery of the ErbB2/HER2 tumor antigen to professional APCs results in effective antitumor immunity. J Immunol. 2005, 174: 5481-5489.CrossRefPubMed
18.
Sloots A, Mastini C, Rohrbach F, Weth R, Curcio C, Burkhardt U, Jager E, Forni G, Cavallo F, Wels WS: DNA vaccines targeting tumor antigens to B7 molecules on antigen-presenting cells induce protective antitumor immunity and delay onset of HER-2/Neu-driven mammary carcinoma. Clin Cancer Res. 2008, 14: 6933-6943. 10.1158/1078-0432.CCR-08-1257.CrossRefPubMed
19.
Wei H, Wang S, Zhang D, Hou S, Qian W, Li B, Guo H, Kou G, He J, Wang H, Guo Y: Targeted delivery of tumor antigens to activated dendritic cells via CD11c molecules induces potent antitumor immunity in mice. Clin Cancer Res. 2009, 15: 4612-4621. 10.1158/1078-0432.CCR-08-3321.CrossRefPubMed
20.
Kim YS, Kim YJ, Lee JM, Han SH, Ko HJ, Park HJ, Pereboev A, Nguyen HH, Kang CY: CD40-targeted recombinant adenovirus significantly enhances the efficacy of antitumor vaccines based on dendritic cells and B cells. Hum Gene Ther. 2010, 21: 1697-1706. 10.1089/hum.2009.202.CrossRefPubMed
21.
Thomann JS, Heurtault B, Weidner S, Braye M, Beyrath J, Fournel S, Schuber F, Frisch B: Antitumor activity of liposomal ErbB2/HER2 epitope peptide-based vaccine constructs incorporating TLR agonists and mannose receptor targeting. Biomaterials. 2011, 32: 4574-4583. 10.1016/j.biomaterials.2011.03.015.CrossRefPubMed
22.
Zizzari IG, Veglia F, Taurino F, Rahimi H, Quaglino E, Belleudi F, Riccardo F, Antonilli M, Napoletano C, Bellati F, Benedetti-Panici P, Torrisi MR, Frati L, Nuti M, Rughetti A: HER2-based recombinant immunogen to target DCs through FcgammaRs for cancer immunotherapy. J Mol Med (Berl). 2011, 89: 1231-1240. 10.1007/s00109-011-0794-7.CrossRef
23.
Jiang W, Swiggard WJ, Heufler C, Peng M, Mirza A, Steinman RM, Nussenzweig MC: The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature. 1995, 375: 151-155. 10.1038/375151a0.CrossRefPubMed
24.
Inaba K, Swiggard WJ, Inaba M, Meltzer J, Mirza A, Sasagawa T, Nussenzweig MC, Steinman RM: Tissue distribution of the DEC-205 protein that is detected by the monoclonal antibody NLDC-145. I. Expression on dendritic cells and other subsets of mouse leukocytes. Cell Immunol. 1995, 163: 148-156. 10.1006/cimm.1995.1109.CrossRefPubMed
25.
Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz V, Trumpfheller C, Yamazaki S, Cheong C, Liu K, Lee HW, Park CG, Steinman RM, Nussenzweig MC: Differential antigen processing by dendritic cell subsets in vivo. Science. 2007, 315: 107-111. 10.1126/science.1136080.CrossRefPubMed
26.
Tacken PJ, de Vries IJM, Torensma R, Figdor CG: Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol. 2007, 7: 790-802. 10.1038/nri2173.CrossRefPubMed
27.
Idoyaga J, Lubkin A, Fiorese C, Lahoud MH, Caminschi I, Huang Y, Rodriguez A, Clausen BE, Park CG, Trumpfheller C, Steinman RM: Comparable T helper 1 (Th1) and CD8 T-cell immnity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proc Natl Acad Sci USA. 2011, 108: 2384-2389. 10.1073/pnas.1019547108.CrossRefPubMedPubMedCentral
28.
Granelli-Piperno A, Pritsker A, Pack M, Shimeliovich I, Arrighi J-F, Park CG, Trumpfheller C, Piguet V, Moran TM, Steinman RM: Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction. J Immunol. 2005, 175: 4265-4273.CrossRefPubMedPubMedCentral
29.
Mahnke K, Guo M, Lee S, Sepulveda H, Swain SL, Nussenzweig M, Steinman RM: The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments. J Cell Biol. 2000, 151: 673-683. 10.1083/jcb.151.3.673.CrossRefPubMedPubMedCentral
30.
Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig MC: Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med. 2001, 194: 769-780. 10.1084/jem.194.6.769.CrossRefPubMedPubMedCentral
31.
Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, Brimnes MK, Moltedo B, Moran TM, Steinman RM: In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med. 2004, 199: 815-824. 10.1084/jem.20032220.CrossRefPubMedPubMedCentral
32.
Wang B, Kuroiwa JM, He LZ, Charalambous A, Keler T, Steinman RM: The human cancer antigen mesothelin is more efficiently presented to the mouse immune system when targeted to the DEC-205/CD205 receptor on dendritic cells. Ann N Y Acad Sci. 2009, 1174: 6-17. 10.1111/j.1749-6632.2009.04933.x.CrossRefPubMedPubMedCentral
33.
Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM: Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med. 2002, 196: 1627-1638. 10.1084/jem.20021598.CrossRefPubMedPubMedCentral
34.
Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM: Dendritic cells require a systemic type I interferon response to induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med. 2009, 206: 1589-1602. 10.1084/jem.20090247.CrossRefPubMedPubMedCentral
35.
Caskey M, Lefebvre F, Filali-Mouhim A, Cameron MJ, Goulet JP, Haddad EK, Breton G, Trumpfheller C, Pollak S, Shimeliovich I, Duque-Alarcon A, Pan L, Nelkenbaum A, Salazar AM, Schlesinger SJ, Steinman RM, Sekaly RP: Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J Exp Med. 2011, 208: 2357-2366. 10.1084/jem.20111171.CrossRefPubMedPubMedCentral
36.
Darrah PA, Patel DT, De Luca PM, Lindsay RW, Davey DF, Flynn BJ, Hoff ST, Andersen P, Reed SG, Morris SL, Roederer M, Seder RA: Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med. 2007, 13: 843-850. 10.1038/nm1592.CrossRefPubMed
37.
Cornell CJ, Smith KA, Cornwell GG, Burke GP, McIntyre OR: Sytemic effects of intravenous polyriboinosinic-polyribocytidylic acid in man. J Natl Cancer Inst. 1976, 57: 1211-1216.PubMed
38.
Morse MA, Chapman R, Powderly J, Blackwell KL, Keler T, Green J, Riggs R, He LZ, Ramakrishna V, Vitale L, Zhao B, Hobeika A, Osada T, Davis TA, Clay TM, Lyerly HK: Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self antigens in cancer patients. Clin Cancer Res. 2011, 17: 4844-4853. 10.1158/1078-0432.CCR-11-0891.CrossRefPubMedPubMedCentral
39.
Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, Zeh H, Holtzman MP, Reinhart TA, Whiteside TL, Butterfield LH, Hamilton RL, Potter DM, Pollack IF, Salazar AM, Lieberman FS: Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011, 29: 330-336. 10.1200/JCO.2010.30.7744.CrossRefPubMed
40.
Prins RM, Soto H, Konkankit V, Odesa SK, Eskin A, Yong WH, Nelson SF, Liau LM: Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res. 2011, 17: 1603-1615. 10.1158/1078-0432.CCR-10-2563.CrossRefPubMed
41.
Rosenfeld MR, Chamberlain MC, Grossman SA, Peereboom DM, Lesser GJ, Batchelor TT, Desideri S, Salazar AM, Ye X: A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma. Neuro Oncol. 2010, 12: 1071-1077. 10.1093/neuonc/noq071.CrossRefPubMedPubMedCentral
42.
Trumpfheller C, Finke JS, Lopez CB, Moran TM, Moltedo B, Soares H, Huang Y, Schlesinger SJ, Park CG, Nussenzweig MC, Granelli-Piperno A, Steinman RM: Intensified and protective CD4+ T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. J Exp Med. 2006, 203: 607-617. 10.1084/jem.20052005.CrossRefPubMedPubMedCentral
43.
Rongcun Y, Salazar-Onfray F, Charo J, Malmberg KJ, Evrin K, Maes H, Kono K, Hising C, Petersson M, Larsson O, Lan L, Appella E, Sette A, Celis E, Kiessling R: Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas. J Immunol. 1999, 163: 1037-1044.PubMed
44.
Gritzapis AD, Mahaira LG, Perez SA, Cacoullos NT, Papamichail M, Baxevanis CN: Vaccination with human HER-2/neu (435-443) CTL peptide induces effective antitumor immunity against HER-2/neu-expressing tumor cells in vivo. Cancer Res. 2006, 66: 5452-5460. 10.1158/0008-5472.CAN-05-4018.CrossRefPubMed
45.
Gu XG, Schmitt M, Hiasa A, Nagata Y, Ikeda H, Sasaki Y, Akiyoshi K, Sunamoto J, Nakamura H, Kuribayashi K, Shiku H: A novel hydrophobized polysaccharide/oncoprotein complex vaccine induces in vitro and in vivo cellular and humoral immune responses against HER2-expressing murine sarcomas. Cancer Res. 1998, 58: 3385-3390.PubMed
46.
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F: Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006, 313: 1960-1964. 10.1126/science.1129139.CrossRefPubMed
47.
Camus M, Tosolini M, Mlecnik B, Pages F, Kirilovsky A, Berger A, Costes A, Bindea G, Charoentong P, Bruneval P, Trajanoski Z, Fridman WH, Galon J: Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res. 2009, 69: 2685-2693. 10.1158/0008-5472.CAN-08-2654.CrossRefPubMed
48.
Trumpfheller C, Caskey M, Nchinda G, Longhi MP, Mizenina O, Huang Y, Schlesinger SJ, Colonna M, Steinman RM: The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci USA. 2008, 105: 2574-2579. 10.1073/pnas.0711976105.CrossRefPubMedPubMedCentral
49.
Pardoll DM, Topalian SL: The role of CD4+ T cell responses in antitumor immunity. Curr Opin Immunol. 1998, 10: 588-594. 10.1016/S0952-7915(98)80228-8.CrossRefPubMed
50.
Castellino F, Germain RN: Cooperation between CD4+ and CD8+ T cells: when, where, and how. Annu Rev Immunol. 2006, 24: 519-540. 10.1146/annurev.immunol.23.021704.115825.CrossRefPubMed
51.
Bos R, Sherman LA: CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res. 2010, 70: 8368-8377. 10.1158/0008-5472.CAN-10-1322.CrossRefPubMedPubMedCentral
52.
Knutson KL, Schiffman K, Cheever MA, Disis ML: Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity. Clin Cancer Res. 2002, 8: 1014-1018.PubMed
53.
Cohen PA, Peng L, Plautz GE, Kim JA, Weng DE, Shu S: CD4+ T cells in adoptive immunotherapy and the indirect mechanism of tumor rejection. Crit Rev Immunol. 2000, 20: 17-56.CrossRefPubMed
54.
Corthay A, Skovseth DK, Lundin KU, Rosjo E, Omholt H, Hofgaard PO, Haraldsen G, Bogen B: Primary antitumor immune response mediated by CD4+ T cells. Immunity. 2005, 22: 371-383. 10.1016/j.immuni.2005.02.003.CrossRefPubMed
55.
Vanderlugt CL, Miller SD: Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol. 2002, 2: 85-95. 10.1038/nri724.CrossRefPubMed
56.
Perez-Diez A, Joncker NT, Choi K, Chan WF, Anderson CC, Lantz O, Matzinger P: CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood. 2007, 109: 5346-5354. 10.1182/blood-2006-10-051318.CrossRefPubMedPubMedCentral
57.
Quezada S, Simpson T, Peggs K, Merghoub T, Vider J, Fan X, Blasberg R, Yagita H, Muranski P, Antony P, Restifo N, Allison J: Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med. 2010, 207: 637-650. 10.1084/jem.20091918.CrossRefPubMedPubMedCentral
58.
Xie Y, Akpinarli A, Maris C, Hipkiss EL, Lane M, Kwon EK, Muranski P, Restifo NP, Antony PA: Naive tumor-specific CD4+ T cells differentiated in vivo eradicate established melanoma. J Exp Med. 2010, 207: 651-667. 10.1084/jem.20091921.CrossRefPubMedPubMedCentral
59.
Mahnke K, Qian Y, Fondel S, Brueck J, Becker C, Enk AH: Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice. Cancer Res. 2005, 65: 7007-7012. 10.1158/0008-5472.CAN-05-0938.CrossRefPubMed
60.
Bozzacco L, Trumpfheller C, Huang Y, Longhi MP, Shimeliovich I, Schauer JD, Park CG, Steinman RM: HIV gag protein is efficiently cross-presented when targeted with an antibody towards the DEC-205 receptor in Flt3 ligand-mobilized murine DC. Eur J Immunol. 2010, 40: 36-46.CrossRefPubMedPubMedCentral
61.
Reilly RT, Gottlieb MB, Ercolini AM, Machiels JP, Kane CE, Okoye FI, Muller WJ, Dixon KH, Jaffee EM: HER-2/neu is a tumor rejection target in tolerized HER-2/neu transgenic mice. Cancer Res. 2000, 60: 3569-3576.PubMed
Metadata
Title
Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice
Authors
Bei Wang
Neeha Zaidi
Li-Zhen He
Li Zhang
Janelle MY Kuroiwa
Tibor Keler
Ralph M Steinman
Publication date
01-04-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3135

Other articles of this Issue 2/2012

Breast Cancer Research 2/2012 Go to the issue

Viewpoint

BRCA1 as a tumor suppressor linked to the regulation of epigenetic states: keeping oncomiRs under control

Research article

Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers

Research article

Effects of a pre-visit educational website on information recall and needs fulfilment in breast cancer genetic counselling, a randomized controlled trial

Research article

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

Research article

Immunohistochemical detection of Polo-like kinase-1 (PLK1) in primary breast cancer is associated with TP53mutation and poor clinical outcome

Research article

Gene expression in extratumoral microenvironment predicts clinical outcome in breast cancer patients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits