Progress in Vaccine Therapies for Breast Cancer

  • Xiaoyu LiEmail author
  • Xia Bu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1026)


Therapeutic cancer vaccines aim to treat pre-existing cancer by boosting the patient’s own immune system, which is an attractive strategy for cancer treatment. The cancer vaccines have mainly been designed to elicit antitumor T-cell immune responses that recognize and eradicate cancer. The advantages of cancer immunotherapy with cancer vaccines include a) high specificity of tumor antigen, b) minimal vaccine-related adverse events, and c) long-lasting immunity boosted by cancer vaccine which is important to control tumor relapse. In this chapter, we discuss identification of tumor antigens in breast cancer (e.g., cancer-testis antigens, neoantigens, HER2/neu, MUC1), the vaccine delivery systems utilized in breast cancer treatment (e.g., peptide vaccines, dendritic cell-based vaccines, and whole tumor cell-based vaccines), as well as clinical trials with therapeutic breast cancer vaccines. Moreover, new-generation clinical trials of breast cancer vaccines will aim at employing personalized vaccines designed to harness robust immune response to a custom-made neoantigen in the patient with breast cancer. Combination of vaccination and other forms of cancer therapy such as chemotherapy, radiotherapy, targeted therapy with monoclonal antibody, or immune checkpoint blockade will be required to achieve potent and durable antitumor clinical benefits.


Breast cancer Cancer vaccines Cancer immunotherapy Clinical trials 



Xiaoyu Li is supported by a grant from National Natural Science Foundation of China (grant number: NSFC 81670163).


  1. 1.
    Greten TF, Jaffee EM (1999) Cancer vaccines. J Clin Oncol 17(3):1047–1060. doi: 10.1200/JCO.1999.17.3.1047 CrossRefPubMedGoogle Scholar
  2. 2.
    Boon T, Coulie PG, Van den Eynde B (1997) Tumor antigens recognized by T cells. Immunol Today 18(6):267–268CrossRefPubMedGoogle Scholar
  3. 3.
    Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 188:22–32CrossRefPubMedGoogle Scholar
  4. 4.
    Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5(8):615–625. doi: 10.1038/nrc1669 CrossRefPubMedGoogle Scholar
  5. 5.
    van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254(5038):1643–1647CrossRefPubMedGoogle Scholar
  6. 6.
    Traversari C, van der Bruggen P, Luescher IF, Lurquin C, Chomez P, Van Pel A, De Plaen E, Amar-Costesec A, Boon T (1992) A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E. J Exp Med 176(5):1453–1457CrossRefPubMedGoogle Scholar
  7. 7.
    Chen YT, Scanlan MJ, Sahin U, Tureci O, Gure AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old LJ (1997) A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A 94(5):1914–1918CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Boel P, Wildmann C, Sensi ML, Brasseur R, Renauld JC, Coulie P, Boon T, van der Bruggen P (1995) BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 2(2):167–175CrossRefPubMedGoogle Scholar
  9. 9.
    De Backer O, Arden KC, Boretti M, Vantomme V, De Smet C, Czekay S, Viars CS, De Plaen E, Brasseur F, Chomez P, Van den Eynde B, Boon T, van der Bruggen P (1999) Characterization of the GAGE genes that are expressed in various human cancers and in normal testis. Cancer Res 59(13):3157–3165PubMedGoogle Scholar
  10. 10.
    Gaugler B, Van den Eynde B, van der Bruggen P, Romero P, Gaforio JJ, De Plaen E, Lethe B, Brasseur F, Boon T (1994) Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J Exp Med 179(3):921–930CrossRefPubMedGoogle Scholar
  11. 11.
    Russo V, Traversari C, Verrecchia A, Mottolese M, Natali PG, Bordignon C (1995) Expression of the MAGE gene family in primary and metastatic human breast cancer: implications for tumor antigen-specific immunotherapy. Int J Cancer 64(3):216–221CrossRefPubMedGoogle Scholar
  12. 12.
    Fujie T, Mori M, Ueo H, Sugimachi K, Akiyoshi T (1997) Expression of MAGE and BAGE genes in Japanese breast cancers. Ann Oncol 8(4):369–372CrossRefPubMedGoogle Scholar
  13. 13.
    Egland KA, Kumar V, Duray P, Pastan I (2002) Characterization of overlapping XAGE-1 transcripts encoding a cancer testis antigen expressed in lung, breast, and other types of cancers. Mol Cancer Ther 1(7):441–450PubMedGoogle Scholar
  14. 14.
    Badovinac Crnjevic T, Spagnoli G, Juretic A, Jakic-Razumovic J, Podolski P, Saric N (2012) High expression of MAGE-A10 cancer-testis antigen in triple-negative breast cancer. Med Oncol 29(3):1586–1591. doi: 10.1007/s12032-011-0120-9 CrossRefPubMedGoogle Scholar
  15. 15.
    Chen YT, Ross DS, Chiu R, Zhou XK, Chen YY, Lee P, Hoda SA, Simpson AJ, Old LJ, Caballero O, Neville AM (2011) Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers. PLoS One 6(3):e17876. doi: 10.1371/journal.pone.0017876 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Curigliano G, Viale G, Ghioni M, Jungbluth AA, Bagnardi V, Spagnoli GC, Neville AM, Nole F, Rotmensz N, Goldhirsch A (2011) Cancer-testis antigen expression in triple-negative breast cancer. Ann Oncol 22(1):98–103. doi: 10.1093/annonc/mdq325 CrossRefPubMedGoogle Scholar
  17. 17.
    Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244(4905):707–712CrossRefPubMedGoogle Scholar
  18. 18.
    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. doi: 10.1007/s00262-003-0475-7 CrossRefPubMedGoogle Scholar
  19. 19.
    Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB et al (1994) Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 54(1):16–20PubMedGoogle Scholar
  20. 20.
    Peoples GE, Goedegebuure PS, Smith R, Linehan DC, Yoshino I, Eberlein TJ (1995) Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci U S A 92(2):432–436CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Disis ML, Shiota FM, Cheever MA (1998) Human HER-2/neu protein immunization circumvents tolerance to rat neu: a vaccine strategy for ‘self’ tumour antigens. Immunology 93(2):192–199CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Disis ML, Grabstein KH, Sleath PR, Cheever MA (1999) Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide-based vaccine. Clin Cancer Res 5(6):1289–1297PubMedGoogle Scholar
  23. 23.
    Kimura T, McKolanis JR, Dzubinski LA, Islam K, Potter DM, Salazar AM, Schoen RE, Finn OJ (2013) MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila) 6(1):18–26. doi: 10.1158/1940-6207.CAPR-12-0275 CrossRefGoogle Scholar
  24. 24.
    Weiner LM, Surana R, Murray J (2010) Vaccine prevention of cancer: can endogenous antigens be targeted? Cancer Prev Res (Phila) 3(4):410–415. doi: 10.1158/1940-6207.CAPR-10-0040 CrossRefGoogle Scholar
  25. 25.
    Kovjazin R, Horn G, Smorodinsky NI, Shapira MY, Carmon L (2014) Cell surface-associated anti-MUC1-derived signal peptide antibodies: implications for cancer diagnostics and therapy. PLoS One 9(1):e85400. doi: 10.1371/journal.pone.0085400 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Kohlgraf KG, Gawron AJ, Higashi M, VanLith ML, Shen X, Caffrey TC, Anderson JM, Hollingsworth MA (2004) Tumor-specific immunity in MUC1.Tg mice induced by immunization with peptide vaccines from the cytoplasmic tail of CD227 (MUC1). Cancer Immunol Immunother 53(12):1068–1084CrossRefPubMedGoogle Scholar
  27. 27.
    Chen D, Xia J, Tanaka Y, Chen H, Koido S, Wernet O, Mukherjee P, Gendler SJ, Kufe D, Gong J (2003) Immunotherapy of spontaneous mammary carcinoma with fusions of dendritic cells and mucin 1-positive carcinoma cells. Immunology 109(2):300–307CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ding L, Lalani EN, Reddish M, Koganty R, Wong T, Samuel J, Yacyshyn MB, Meikle A, Fung PY, Taylor-Papadimitriou J et al (1993) Immunogenicity of synthetic peptides related to the core peptide sequence encoded by the human MUC1 mucin gene: effect of immunization on the growth of murine mammary adenocarcinoma cells transfected with the human MUC1 gene. Cancer Immunol Immunother 36(1):9–17CrossRefPubMedGoogle Scholar
  29. 29.
    Apostolopoulos V, Xing PX, McKenzie IF (1994) Murine immune response to cells transfected with human MUC1: immunization with cellular and synthetic antigens. Cancer Res 54(19):5186–5193PubMedGoogle Scholar
  30. 30.
    Zhang S, Graeber LA, Helling F, Ragupathi G, Adluri S, Lloyd KO, Livingston PO (1996) Augmenting the immunogenicity of synthetic MUC1 peptide vaccines in mice. Cancer Res 56(14):3315–3319PubMedGoogle Scholar
  31. 31.
    Acres RB, Hareuveni M, Balloul JM, Kieny MP (1993) Vaccinia virus MUC1 immunization of mice: immune response and protection against the growth of murine tumors bearing the MUC1 antigen. J Immunother Emphasis Tumor Immunol 14(2):136–143CrossRefPubMedGoogle Scholar
  32. 32.
    Joffroy CM, Buck MB, Stope MB, Popp SL, Pfizenmaier K, Knabbe C (2010) Antiestrogens induce transforming growth factor beta-mediated immunosuppression in breast cancer. Cancer Res 70(4):1314–1322. doi: 10.1158/0008-5472.CAN-09-3292 CrossRefPubMedGoogle Scholar
  33. 33.
    Castle JC, Kreiter S, Diekmann J, Lower M, van de Roemer N, de Graaf J, Selmi A, Diken M, Boegel S, Paret C, Koslowski M, Kuhn AN, Britten CM, Huber C, Tureci O, Sahin U (2012) Exploiting the mutanome for tumor vaccination. Cancer Res 72(5):1081–1091. doi: 10.1158/0008-5472.CAN-11-3722 CrossRefPubMedGoogle Scholar
  34. 34.
    Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, Lin JC, Teer JK, Cliften P, Tycksen E, Samuels Y, Rosenberg SA (2013) Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med 19(6):747–752. doi: 10.1038/nm.3161 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Wick DA, Webb JR, Nielsen JS, Martin SD, Kroeger DR, Milne K, Castellarin M, Twumasi-Boateng K, Watson PH, Holt RA, Nelson BH (2014) Surveillance of the tumor mutanome by T cells during progression from primary to recurrent ovarian cancer. Clin Cancer Res 20(5):1125–1134. doi: 10.1158/1078-0432.CCR-13-2147 CrossRefPubMedGoogle Scholar
  36. 36.
    Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314(5797):268–274. doi: 10.1126/science.1133427 CrossRefPubMedGoogle Scholar
  37. 37.
    Segal NH, Parsons DW, Peggs KS, Velculescu V, Kinzler KW, Vogelstein B, Allison JP (2008) Epitope landscape in breast and colorectal cancer. Cancer Res 68(3):889–892. doi: 10.1158/0008-5472.CAN-07-3095 CrossRefPubMedGoogle Scholar
  38. 38.
    Thompson JA, Grunert F, Zimmermann W (1991) Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J Clin Lab Anal 5(5):344–366CrossRefPubMedGoogle Scholar
  39. 39.
    Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, Mellman I, Prindiville SA, Viner JL, Weiner LM, Matrisian LM (2009) The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res 15(17):5323–5337. doi: 10.1158/1078-0432.CCR-09-0737 CrossRefPubMedGoogle Scholar
  40. 40.
    Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, Hofmann WK, Uharek L, Thiel E, Scheibenbogen C (2009) A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood 113(26):6541–6548. doi: 10.1182/blood-2009-02-202598 CrossRefPubMedGoogle Scholar
  41. 41.
    Topalian SL, Gonzales MI, Parkhurst M, Li YF, Southwood S, Sette A, Rosenberg SA, Robbins PF (1996) Melanoma-specific CD4+ T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes. J Exp Med 183(5):1965–1971CrossRefPubMedGoogle Scholar
  42. 42.
    Manici S, Sturniolo T, Imro MA, Hammer J, Sinigaglia F, Noppen C, Spagnoli G, Mazzi B, Bellone M, Dellabona P, Protti MP (1999) Melanoma cells present a MAGE-3 epitope to CD4(+) cytotoxic T cells in association with histocompatibility leukocyte antigen DR11. J Exp Med 189(5):871–876CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Pieper R, Christian RE, Gonzales MI, Nishimura MI, Gupta G, Settlage RE, Shabanowitz J, Rosenberg SA, Hunt DF, Topalian SL (1999) Biochemical identification of a mutated human melanoma antigen recognized by CD4(+) T cells. J Exp Med 189(5):757–766CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Wang RF, Wang X, Rosenberg SA (1999) Identification of a novel major histocompatibility complex class II-restricted tumor antigen resulting from a chromosomal rearrangement recognized by CD4(+) T cells. J Exp Med 189(10):1659–1668CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Chiari R, Hames G, Stroobant V, Texier C, Maillere B, Boon T, Coulie PG (2000) Identification of a tumor-specific shared antigen derived from an Eph receptor and presented to CD4 T cells on HLA class II molecules. Cancer Res 60(17):4855–4863PubMedGoogle Scholar
  46. 46.
    Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, Knutson KL, Schiffman K (2002) Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol 20(11):2624–2632. doi: 10.1200/JCO.2002.06.171 CrossRefPubMedGoogle Scholar
  47. 47.
    Disis ML, Schiffman K, Guthrie K, Salazar LG, Knutson KL, Goodell V, dela Rosa C, Cheever MA (2004) Effect of dose on immune response in patients vaccinated with an her-2/neu intracellular domain protein--based vaccine. J Clin Oncol 22 (10):1916–1925. doi: 10.1200/JCO.2004.09.005
  48. 48.
    Disis ML, Goodell V, Schiffman K, Knutson KL (2004) Humoral epitope-spreading following immunization with a HER-2/neu peptide based vaccine in cancer patients. J Clin Immunol 24(5):571–578. doi: 10.1023/B:JOCI.0000040928.67495.52 CrossRefPubMedGoogle Scholar
  49. 49.
    Knutson KL, Schiffman K, Disis ML (2001) Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients. J Clin Invest 107(4):477–484. doi: 10.1172/JCI11752 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Bowne WB, Wolchok JD, Hawkins WG, Srinivasan R, Gregor P, Blachere NE, Moroi Y, Engelhorn ME, Houghton AN, Lewis JJ (1999) Injection of DNA encoding granulocyte-macrophage colony-stimulating factor recruits dendritic cells for immune adjuvant effects. Cytokines Cell Mol Ther 5(4):217–225PubMedGoogle Scholar
  51. 51.
    Disis ML, Bernhard H, Shiota FM, Hand SL, Gralow JR, Huseby ES, Gillis S, Cheever MA (1996) Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines. Blood 88(1):202–210PubMedGoogle Scholar
  52. 52.
    Benavides LC, Sears AK, Gates JD, Clifton GT, Clive KS, Carmichael MG, Holmes JP, Mittendorf EA, Ponniah S, Peoples GE (2011) Comparison of different HER2/neu vaccines in adjuvant breast cancer trials: implications for dosing of peptide vaccines. Expert Rev Vaccines 10(2):201–210. doi: 10.1586/erv.10.167 CrossRefPubMedGoogle Scholar
  53. 53.
    Tagliamonte M, Petrizzo A, Tornesello ML, Buonaguro FM, Buonaguro L (2014) Antigen-specific vaccines for cancer treatment. Hum Vaccin Immunother 10(11):3332–3346. doi: 10.4161/21645515.2014.973317 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Mittendorf EA, Clifton GT, Holmes JP, Schneble E, van Echo D, Ponniah S, Peoples GE (2014) Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol 25(9):1735–1742. doi: 10.1093/annonc/mdu211 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Peoples GE, Holmes JP, Hueman MT, Mittendorf EA, Amin A, Khoo S, Dehqanzada ZA, Gurney JM, Woll MM, Ryan GB, Storrer CE, Craig D, Ioannides CG, Ponniah S (2008) Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. military cancer institute clinical trials group study I-01 and I-02. Clin Cancer Res 14(3):797–803. doi: 10.1158/1078-0432.CCR-07-1448 CrossRefPubMedGoogle Scholar
  56. 56.
    Mittendorf EA, Storrer CE, Foley RJ, Harris K, Jama Y, Shriver CD, Ponniah S, Peoples GE (2006) Evaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast cancer vaccine trial. Cancer 106(11):2309–2317. doi: 10.1002/cncr.21849 CrossRefPubMedGoogle Scholar
  57. 57.
    Knutson KL, Disis ML (2005) Augmenting T helper cell immunity in cancer. Curr Drug Targets Immune Endocr Metabol Disord 5(4):365–371CrossRefPubMedGoogle Scholar
  58. 58.
    Knutson KL, Disis ML (2005) Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother 54(8):721–728. doi: 10.1007/s00262-004-0653-2 CrossRefPubMedGoogle Scholar
  59. 59.
    Holmes JP, Benavides LC, Gates JD, Carmichael MG, Hueman MT, Mittendorf EA, Murray JL, Amin A, Craig D, von Hofe E, Ponniah S, Peoples GE (2008) Results of the first phase I clinical trial of the novel II-key hybrid preventive HER-2/neu peptide (AE37) vaccine. J Clin Oncol 26(20):3426–3433. doi: 10.1200/JCO.2007.15.7842 CrossRefPubMedGoogle Scholar
  60. 60.
    Mittendorf EA, Ardavanis A, Litton JK, Shumway NM, Hale DF, Murray JL, Perez SA, Ponniah S, Baxevanis CN, Papamichail M, Peoples GE (2016) Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence. Oncotarget 7 (40):66192–66201. doi:10.18632/oncotarget.11751
  61. 61.
    Julien S, Picco G, Sewell R, Vercoutter-Edouart AS, Tarp M, Miles D, Clausen H, Taylor-Papadimitriou J, Burchell JM (2009) Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model. Br J Cancer 100(11):1746–1754. doi: 10.1038/sj.bjc.6605083 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Zhang S, Walberg LA, Ogata S, Itzkowitz SH, Koganty RR, Reddish M, Gandhi SS, Longenecker BM, Lloyd KO, Livingston PO (1995) Immune sera and monoclonal antibodies define two configurations for the sialyl Tn tumor antigen. Cancer Res 55(15):3364–3368PubMedGoogle Scholar
  63. 63.
    Gilewski TA, Ragupathi G, Dickler M, Powell S, Bhuta S, Panageas K, Koganty RR, Chin-Eng J, Hudis C, Norton L, Houghton AN, Livingston PO (2007) Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21. Clin Cancer Res 13(10):2977–2985. doi: 10.1158/1078-0432.CCR-06-2189 CrossRefPubMedGoogle Scholar
  64. 64.
    Finn OJ, Jerome KR, Henderson RA, Pecher G, Domenech N, Magarian-Blander J, Barratt-Boyes SM (1995) MUC-1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev 145:61–89CrossRefPubMedGoogle Scholar
  65. 65.
    Graham RA, Burchell JM, Taylor-Papadimitriou J (1996) The polymorphic epithelial mucin: potential as an immunogen for a cancer vaccine. Cancer Immunol Immunother 42(2):71–80CrossRefPubMedGoogle Scholar
  66. 66.
    Blixt O, Bueti D, Burford B, Allen D, Julien S, Hollingsworth M, Gammerman A, Fentiman I, Taylor-Papadimitriou J, Burchell JM (2011) Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis. Breast Cancer Res 13(2):R25. doi: 10.1186/bcr2841 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Hiltbold EM, Ciborowski P, Finn OJ (1998) Naturally processed class II epitope from the tumor antigen MUC1 primes human CD4+ T cells. Cancer Res 58(22):5066–5070PubMedGoogle Scholar
  68. 68.
    Hiltbold EM, Alter MD, Ciborowski P, Finn OJ (1999) Presentation of MUC1 tumor antigen by class I MHC and CTL function correlate with the glycosylation state of the protein taken up by dendritic cells. Cell Immunol 194(2):143–149. doi: 10.1006/cimm.1999.1512 CrossRefPubMedGoogle Scholar
  69. 69.
    Siroy A, Abdul-Karim FW, Miedler J, Fong N, Fu P, Gilmore H, Baar J (2013) MUC1 is expressed at high frequency in early-stage basal-like triple-negative breast cancer. Hum Pathol 44(10):2159–2166. doi: 10.1016/j.humpath.2013.04.010 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Apostolopoulos V, Pietersz GA, Tsibanis A, Tsikkinis A, Drakaki H, Loveland BE, Piddlesden SJ, Plebanski M, Pouniotis DS, Alexis MN, McKenzie IF, Vassilaros S (2006) Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]. Breast Cancer Res 8(3):R27. doi: 10.1186/bcr1505 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252. doi: 10.1038/32588 CrossRefPubMedGoogle Scholar
  72. 72.
    Greenberg NM, Anderson JW, Hsueh AJ, Nishimori K, Reeves JJ, deAvila DM, Ward DN, Rosen JM (1991) Expression of biologically active heterodimeric bovine follicle-stimulating hormone in milk of transgenic mice. Proc Natl Acad Sci U S A 88(19):8327–8331CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Rohrbach F, Weth R, Kursar M, Sloots A, Mittrucker HW, Wels WS (2005) Targeted delivery of the ErbB2/HER2 tumor antigen to professional APCs results in effective antitumor immunity. J Immunol 174(9):5481–5489CrossRefPubMedGoogle Scholar
  74. 74.
    Nabekura T, Nagasawa T, Nakauchi H, Onodera M (2008) An immunotherapy approach with dendritic cells genetically modified to express the tumor-associated antigen, HER2. Cancer Immunol Immunother 57(5):611–622. doi: 10.1007/s00262-007-0399-8 CrossRefPubMedGoogle Scholar
  75. 75.
    Gabrilovich DI, Nadaf S, Corak J, Berzofsky JA, Carbone DP (1996) Dendritic cells in antitumor immune responses. II. Dendritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors. Cell Immunol 170(1):111–119. doi: 10.1006/cimm.1996.0140 CrossRefPubMedGoogle Scholar
  76. 76.
    Fong L, Brockstedt D, Benike C, Wu L, Engleman EG (2001) Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 166(6):4254–4259CrossRefPubMedGoogle Scholar
  77. 77.
    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):3340–3345PubMedGoogle Scholar
  78. 78.
    Palucka K, Banchereau J (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12(4):265–277. doi: 10.1038/nrc3258 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 96(9):3102–3108PubMedGoogle Scholar
  80. 80.
    Czerniecki BJ, Koski GK, Koldovsky U, Xu S, Cohen PA, Mick R, Nisenbaum H, Pasha T, Xu M, Fox KR, Weinstein S, Orel SG, Vonderheide R, Coukos G, DeMichele A, Araujo L, Spitz FR, Rosen M, Levine BL, June C, Zhang PJ (2007) Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Cancer Res 67(4):1842–1852. doi: 10.1158/0008-5472.CAN-06-4038 CrossRefPubMedGoogle Scholar
  81. 81.
    Lowenfeld L, Mick R, Datta J, Xu S, Fitzpatrick E, Fisher CS, Fox KR, DeMichele A, Zhang PJ, Weinstein SP, Roses RE, Czerniecki BJ (2016) Dendritic cell vaccination enhances immune responses and induces regression of HER2pos DCIS independent of route: results of randomized selection design trial. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-16-1924
  82. 82.
    Sharma A, Koldovsky U, Xu S, Mick R, Roses R, Fitzpatrick E, Weinstein S, Nisenbaum H, Levine BL, Fox K, Zhang P, Koski G, Czerniecki BJ (2012) HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ. Cancer 118(17):4354–4362. doi: 10.1002/cncr.26734 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 90(8):3539–3543CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Dranoff G (2002) GM-CSF-based cancer vaccines. Immunol Rev 188:147–154CrossRefPubMedGoogle Scholar
  85. 85.
    Antonia SJ, Seigne J, Diaz J, Muro-Cacho C, Extermann M, Farmelo MJ, Friberg M, Alsarraj M, Mahany JJ, Pow-Sang J, Cantor A, Janssen W (2002) Phase I trial of a B7-1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma. J Urol 167(5):1995–2000CrossRefPubMedGoogle Scholar
  86. 86.
    Jaffee EM, Hruban RH, Biedrzycki B, Laheru D, Schepers K, Sauter PR, Goemann M, Coleman J, Grochow L, Donehower RC, Lillemoe KD, O’Reilly S, Abrams RA, Pardoll DM, Cameron JL, Yeo CJ (2001) Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J Clin Oncol 19(1):145–156. doi: 10.1200/JCO.2001.19.1.145 CrossRefPubMedGoogle Scholar
  87. 87.
    Soiffer R, Hodi FS, Haluska F, Jung K, Gillessen S, Singer S, Tanabe K, Duda R, Mentzer S, Jaklitsch M, Bueno R, Clift S, Hardy S, Neuberg D, Mulligan R, Webb I, Mihm M, Dranoff G (2003) Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J Clin Oncol 21(17):3343–3350. doi: 10.1200/JCO.2003.07.005 CrossRefPubMedGoogle Scholar
  88. 88.
    Salgia R, Lynch T, Skarin A, Lucca J, Lynch C, Jung K, Hodi FS, Jaklitsch M, Mentzer S, Swanson S, Lukanich J, Bueno R, Wain J, Mathisen D, Wright C, Fidias P, Donahue D, Clift S, Hardy S, Neuberg D, Mulligan R, Webb I, Sugarbaker D, Mihm M, Dranoff G (2003) Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma. J Clin Oncol 21(4):624–630. doi: 10.1200/JCO.2003.03.091 CrossRefPubMedGoogle Scholar
  89. 89.
    Emens LA, Asquith JM, Leatherman JM, Kobrin BJ, Petrik S, Laiko M, Levi J, Daphtary MM, Biedrzycki B, Wolff AC, Stearns V, Disis ML, Ye X, Piantadosi S, Fetting JH, Davidson NE, Jaffee EM (2009) Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. J Clin Oncol 27(35):5911–5918. doi: 10.1200/JCO.2009.23.3494 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Rice J, Ottensmeier CH, Stevenson FK (2008) DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer 8(2):108–120. doi: 10.1038/nrc2326 CrossRefPubMedGoogle Scholar
  91. 91.
    Campos-Perez J, Rice J, Escors D, Collins M, Paterson A, Savelyeva N, Stevenson FK (2013) DNA fusion vaccine designs to induce tumor-lytic CD8+ T-cell attack via the immunodominant cysteine-containing epitope of NY-ESO 1. Int J Cancer 133(6):1400–1407. doi: 10.1002/ijc.28156 CrossRefPubMedGoogle Scholar
  92. 92.
    Rice J, Buchan S, Stevenson FK (2002) Critical components of a DNA fusion vaccine able to induce protective cytotoxic T cells against a single epitope of a tumor antigen. J Immunol 169(7):3908–3913CrossRefPubMedGoogle Scholar
  93. 93.
    Rice J, Elliott T, Buchan S, Stevenson FK (2001) DNA fusion vaccine designed to induce cytotoxic T cell responses against defined peptide motifs: implications for cancer vaccines. J Immunol 167(3):1558–1565CrossRefPubMedGoogle Scholar
  94. 94.
    Zhu D, Williams JN, Rice J, Stevenson FK, Heckels JE, Christodoulides M (2008) A DNA fusion vaccine induces bactericidal antibodies to a peptide epitope from the PorA porin of Neisseria meningitidis. Infect Immun 76(1):334–338. doi: 10.1128/IAI.00943-07 CrossRefPubMedGoogle Scholar
  95. 95.
    Watson MA, Fleming TP (1994) Isolation of differentially expressed sequence tags from human breast cancer. Cancer Res 54(17):4598–4602PubMedGoogle Scholar
  96. 96.
    Tiriveedhi V, Tucker N, Herndon J, Li L, Sturmoski M, Ellis M, Ma C, Naughton M, Lockhart AC, Gao F, Fleming T, Goedegebuure P, Mohanakumar T, Gillanders WE (2014) Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer. Clin Cancer Res 20(23):5964–5975. doi: 10.1158/1078-0432.CCR-14-0059 CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G (2015) Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell 28(6):690–714. doi: 10.1016/j.ccell.2015.10.012 CrossRefPubMedGoogle Scholar
  98. 98.
    Bezu L, Gomes-de-Silva LC, Dewitte H, Breckpot K, Fucikova J, Spisek R, Galluzzi L, Kepp O, Kroemer G (2015) Combinatorial strategies for the induction of immunogenic cell death. Front Immunol 6:187. doi: 10.3389/fimmu.2015.00187 PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of HematologyThe First Affiliated Hospital, Henan University Cancer Center, School of Medicine, Henan UniversityKaifengPeople’s Republic of China
  2. 2.Department of Medical OncologyThe First Affiliated Hospital, Henan University Cancer Center, School of Medicine, Henan UniversityKaifengPeople’s Republic of China

Personalised recommendations