Skip to main content

Advertisement

SpringerLink
Log in

Immunogenic HER-2/neu peptides as tumor vaccines

  • Symposium Paper
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

During the last decade, a large number of tumor-associated antigens (TAA) have been identified, which can be recognized by T cells. This has led to renewed interest in the use of active immunization as a modality for the treatment of cancer. HER-2/neu is a 185-KDa receptor-like glycoprotein that is overexpressed by a variety of tumors including breast, ovarian, lung, prostate and colorectal carcinomata. Several immunogenic HER-2/neu peptides recognized by cytotoxic T lymphocytes (CTL) or helper T lymphocytes (TH) have been identified thus far. Patients with HER-2/neu over-expressing cancers exhibit increased frequencies of peripheral blood T cells recognizing immunogenic HER-2/neu peptides. Various protocols for generating T cell-mediated immune responses specific for HER-2/neu peptides have been examined in pre-clinical models or in clinical trials. Vaccination studies in animals utilizing HER-2/neu peptides have been successful in eliminating tumor growth. In humans, however, although immunological responses have been detected against the peptides used for vaccination, no clinical responses have been described. Because HER-2/neu is a self-antigen, functional immune responses against it may be limited through tolerance mechanisms. Therefore, it would be interesting to determine whether abrogation of tolerance to HER-2/neu using appropriate adjuvants and/or peptide analogs may lead to the development of immune responses to HER-2/neu epitopes that can be of relevance to cancer immunotherapy. Vaccine preparations containing mixtures of HER-2/neu peptides and peptide from other tumor-related antigens might also enhance efficacy of therapeutic vaccination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ahmad-Najad P, Hacke H, Rutz M, Bauer S, Vabulas RM, Wagner H (2002) Bacterial DNA and lipopolysaccharides active Toll-like receptors at distinct cellular compartments. Eur J Immunol 32:1958

    Article  PubMed  Google Scholar 

  2. Amarnath SM, Dyer CE, Ramesh A, Iwuagwu O, Drew PJ, Greenman J (2004) In vitro quantification of the cytotoxic T lymphocyte response against human telomerase reverse transcriptase in breast cancer. Int J Oncol 25:211

    PubMed  CAS  Google Scholar 

  3. Andersen MH, Pedersen LO, Becker JC, Straten PT (2001) Identification of a cytotoxic T lymphocyte reponse to the apoptosis inhibitor protein survirin in cancer patients. Cancer Res 61:869

    PubMed  CAS  Google Scholar 

  4. Anderson BW, Kudelka AD, Honda T, Pollack MS, Gershenson DM, Gillogly MA, Murray JI, Ioannides CG (2000) Induction of determinant spreading and of TH1 responses by in vitro stimulation with HER-2 peptides. Cancer Immunol Immunother 49:459

    Article  PubMed  CAS  Google Scholar 

  5. Baxevanis CN, Gritzapis AD, Tsitsilonis OE, Katsoulas HL, Papamichail M (2002) HER-2/neu-derived epitopes are also recognized by cytotoxic CD3+ CD56+ (Natural killer T) lymphocytes. Int J Cancer 98:864

    Article  PubMed  CAS  Google Scholar 

  6. 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 53:166

    Article  PubMed  CAS  Google Scholar 

  7. Baxevanis CN, Voutsas IF, Tsitsilonis OE, Gritzapis AD, Sotiriadou R, Papamichail M (2000) Tumor-specific CD4+ T lymphocytes from cancer patients are required for optimal induction of cytotoxic T cells against the autologous tumor. J Immunol 164:3902

    PubMed  CAS  Google Scholar 

  8. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987) The foreign antigen binding site and T cell recognition regions of class I histocompatbility antigens. Nature 329:512

    Article  PubMed  CAS  Google Scholar 

  9. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987) Structure of the human class I histocompatibility antigen HLA-A2. Nature 329:506

    Article  PubMed  CAS  Google Scholar 

  10. Blackburn EH (1992) Telomerases. Annu Rev Biochem 61:113

    Article  PubMed  CAS  Google Scholar 

  11. Bownds S, Tong-On P, Rosenberg SA, Parkhurst M (2001) Induction of tumor-reactive cytotoxic T-lymphocytes using a peptide from NY-ESO-1 modified at the carboxy-terminus to enhance HLA-A2.1 binding affinity and stability in solution. J Immunother 24:1

    Article  PubMed  CAS  Google Scholar 

  12. Brossart P, Stuhler G, Flad T, Stevanovic S, Sammensee HG, Kanz L, Brugger W (1998) HER-2/neu-derived peptides are tumor-associated antigens expressed by human renal cell and colon carcinoma lines and are recognized by in vitro induced specific cytotoxic T lymphocytes. Cancer Res 58:732

    PubMed  CAS  Google Scholar 

  13. Castilleja A, Carter D, Efferson CL, Ward NE, Kawano K, Fisk B, Kudelka AP, Gershenson DM, Murray JI, O’Brian CA, Ioannides CG (2002) Induciton of tumor-reactive CTL by C-side chain variants of the CTL epitope HER-2/neu proton-ogene (369-377) selected by molecular modeling of the peptide HLA-A2 complex. J Immunol 169:3545

    PubMed  CAS  Google Scholar 

  14. Celis E, Tsai V, Crimi C, DeMars R, Wentworth PA, Chesnut RW, Grey HM, Sette A, Serra HM (1994) Induction of anti-tumor cytotoxic T lymphocytes in normal humans using primary cultures and synthetic peptide epitopes. Proc Natl Acad Sci USA 91:2105

    PubMed  CAS  Google Scholar 

  15. Chen PW, Ananthaswamy HN (1993) Rejection of K1735 murine melanoma in syngeneic hosts required expression of MHC class I antigens and either class II antigens of IL-2. J Immunol 151:244

    PubMed  CAS  Google Scholar 

  16. D’Amaro J, Houbiers JG, Drijfhout JW, Brandt RMP, Schipper R, Bavinck JN, Melief CJM, Kast WM (1995) A computer program for predicting possible cytotoxic T lymphocyte epitopes based on HLA class I peptide-binding motifs. Hum Immunol 43:13

    Article  PubMed  CAS  Google Scholar 

  17. Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, Knutson KL, Shiffmann 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 20:2624

    Article  PubMed  CAS  Google Scholar 

  18. Disis ML, Rinn K, Knutson KL, Davis D, Caron D, dela Rosa C, Schiffman K (2002) FLt3 ligand as a vaccine adjuvant in association with HER-2/neu peptide-based vaccines in patients with HER-2/neu-overexpressing cancers. Blood 99:2845

    Article  PubMed  CAS  Google Scholar 

  19. Eccles SA (2001) The role c-erbB-2/HER-2/neu in breast cancer progression and metastasis. J Mammary Gland Biol Neoplasia 6:393

    Article  PubMed  CAS  Google Scholar 

  20. Engelhard VH (1994) Structure of peptides associated with MHC class I molecules. Curr Opin Immunol 6:13

    Article  PubMed  CAS  Google Scholar 

  21. Ercolini AM, Machiels J-PH, Chen YC, Slansky JE, Giedlen M, Reilly RT, Jaffee EM (2003) Identification and characterization of the immunodominant rat HER-2/neu MHC class I epitope presented by spontaneous mammary tumor from HER-2/neu-transgenic mice. J Immunol 170:4273

    PubMed  CAS  Google Scholar 

  22. Falk K, Rotzschke O, Stevanovic S, Jung G, Rammensee HG (1991) Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351:290

    Article  PubMed  CAS  Google Scholar 

  23. Farina C, Theil D, Semlinger B, Hohlfeld R, Meinl E (2004) Distinct responses of monocytes to Toll-like receptor ligands and imflammatory cytokines. Int Immunol 16:799

    Article  PubMed  CAS  Google Scholar 

  24. Fisk B, Blevins TL, Wharton JT, Ioannides CG (1995) Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor- specific cytotoxic T lymphocyte lines. J Exp Med 181:2109

    Article  PubMed  CAS  Google Scholar 

  25. Fisk B, Chesak B, Pollack MS, Wharton JT, Ioannides CG (1994) Oligopeptide induction of a cytotoxic T lymphocyte response to HER-2/neu proto-oncogene in vitro. Cell Immunol 157:415

    Article  PubMed  CAS  Google Scholar 

  26. Fisk B, Hudson JM, Kavanagh J, Wharton JT, Murray JL, Ioannides CG, Kudelka AP (1997) Existent proliferative response of peripheral blood mononuclear cells from healthy donors and ovarian cancer patients to HER-2 peptides. Anticancer Res 17:45

    PubMed  CAS  Google Scholar 

  27. Fong L, Brockstedt D, Benike C et al Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy from HER-2/neu-transgenic mice. J Immunol 170:4273

  28. Goodison S, Viars C, Urquidi V (2005) Molecular cytogenetic analysis of a human breast metastasis model: identification of phenotype-specific chromosomal rearrangements. Cancer Genet Cytogenet 156:37

    Article  PubMed  CAS  Google Scholar 

  29. Gritzapis AD, Sotiriadou NN, Papamichail M, Baxevanis CN (2004) Generation of human tumor-specific CTLs in HLA-A2.1 trangenic mice using unfractionated peptides from eluates of human primary breast and ovarian tumors. Cancer Immunol Immunother 53:1027

    Article  PubMed  Google Scholar 

  30. Guy CT, Webmaster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ (1992) Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic diseases. Proc Natl Acad Sci USA 89:10578

    PubMed  CAS  Google Scholar 

  31. Hausmann S, Martin M, Gauthier L, Wucherpfennig K (1999) Structural features of autoreactive TCR that determine the degree of degenerary in peptide recognition. J Immunol 162:338

    PubMed  CAS  Google Scholar 

  32. Hemmi H, Takeuchi O, Kawai T, Kaison T, Sato S, Sanjo H, Mattimoto Hoshino K, Wagner H, Takeda K, Akira SA (2000) Toll-like receptor recognize bacterial DNA. Nature 408:740

    Article  PubMed  CAS  Google Scholar 

  33. Hernandez J, Schoeder P, Blondelle SE, Pons FG, Lone YC, Simora A, Langlade-Demoyen P, Wilson DB, Zanetti M (2004) Antigenicity and immunogenicity of peptide analogues of a low affinity peptide of the human telomerase reverse transcriptase tumor antigen. Eur J Immunol 34:2331

    Article  PubMed  CAS  Google Scholar 

  34. Hirohashi Y, Torigoe T, Maeda A, Nabeta Y, Kamiguchi K, Sato T, Yoda J, Ikeda H, Hirata K, Yamanaka N, Sato N (2002) An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survirin. Clin Cancer Res 8:1731

    PubMed  CAS  Google Scholar 

  35. Hori S, Takahashi T, Sakeguchi S (2003) Control of autoimmunity by naturally arising regulatory CD4+ T cells. Adv Immunol 81:331

    PubMed  CAS  Google Scholar 

  36. Ikeda H, Chamoto K, Tsuji T, Suzuki Y, Wakita D, Takeshima T, Takashi N (2004) The critical role of type-1 innate and acquired immunity in tumor immunotherapy. Cancer Sci 95:697

    Article  PubMed  CAS  Google Scholar 

  37. Ito T, Shiraki K, Sugomoto K, Yamanaka T, Fujikawa K, Ito M, Takase K, Moriyama M, Kawano H, Hayashida M, Nakano Y, Suzuki A (2000) Survirin promotes cell proliferation in human hepatocellular carcinoma. Hepatology 31:1080

    Article  PubMed  CAS  Google Scholar 

  38. Kageshita T, Hirai S, Ono T, Hicklin DJ, Ferrone S (1999) Down-regulation of HLA class I antigen-processing molecules in malignant melanoma: association with disease progression. Am J Pathol 154:745

    PubMed  CAS  Google Scholar 

  39. Kawai K, Ohashi PS (1995) Immunological function of a defined T cell population tolerized to low-affinity self antigens. Nature 374:68

    Article  PubMed  CAS  Google Scholar 

  40. Kawakami Y, Eliyadu S, Sakaguchi K, Robbins PF, Rivoltini I, Yannelli JR, Apella E, Rosenberg SA (1994) Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med 180:347

    Article  PubMed  CAS  Google Scholar 

  41. Kawashima I, Hudson SJ, Tsai V, Southwood S, Takesako K, Appella E, Sette A, Celis E (1998) The multiepitope approach for immunotherapy of cancer: identification of several CTL epitopes from various tumor-associated antigens expressed on solid epithelial tumors. Hum Immunol 59:1

    Article  PubMed  CAS  Google Scholar 

  42. Kawashima I, Tsai V, Southwood S, Takesako K, Sette A, Celis E (1999) Identification of HLA-A3-restricted cytotoxic T lymphocytes epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. Cancer Res 59:431

    PubMed  CAS  Google Scholar 

  43. Keogh E, Fikes J, Southwood S, Celis E, Chesnut R, Sette A (2001) Identification of new epitopes from four different tumor-associated antigens: recognition of naturally processed epitopes correlates with HLA-A*0201-binding affinity. J Immunol 167:787

    PubMed  CAS  Google Scholar 

  44. Kessler JH, Beekman NJ, Bres-Vloemans SA, Verdijk P, van Veelen PA, Kloosterman-Joosten AM, Vissers DC, ten Bosch GJ, Kester MG, Sijts A, Drijfhout JW, Ossendorp F, Offringa R, Melief CJM (2001) Efficient identification of novel HLA-A*0201-presented cytotoxic T lymphocyte epitopes in the widely expressed tumor antigen PRAME by proteasome-mediated digestion analysis. J Exp Med 193:73

    Article  PubMed  CAS  Google Scholar 

  45. Kiessling R, Wel WZ, Herrmann F, Lindencrona JA, Cheudhury A, Kono K, Seliger B (2002) Cellular immunity to the HER-2/neu protooncogene. Adv Cancer Res 85:101

    Article  PubMed  CAS  Google Scholar 

  46. Kim NW (1997) Clinical implications of telomerase in cancer. Eur J Cancer 33:781

    Article  PubMed  CAS  Google Scholar 

  47. Knutson KL, Shiftmann K, Cheever MA, Disis ML (2002) Immunization of cancer patients with a HER-2/neu. HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity. Clin Cancer Res 8:1014

    PubMed  CAS  Google Scholar 

  48. Knutson KL, Shiftmann K, Disis ML (2001) Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity to cancer patients. J Clin Invest 107: 477

    Article  PubMed  CAS  Google Scholar 

  49. Kobayashi H, Wood M, Song Y, Appelle E, Celis E (2000) Defining promiscuous MHC class II helper T-cell epitopes for HER-2/neu tumor antigen. Cancer Res 60:52258

    Google Scholar 

  50. Kondo A, Sidney J, Southwood S, del Guercio MF, Appella E, Sakamoto H, Celis E, Grey HM, Chesnut RW, Kubo RT (1995) Prominent roles of secondary anchor residues in peptide binding to HLA-A24 human class I molecules. J Immunol 155:4307

    PubMed  CAS  Google Scholar 

  51. Kono K, Rongcun Y, Charo J, Ichihara F, Celis E, Sette A, Appellia E, Sekikawa T, Matshumoto Y, Kiessling R (1998) Identification of HER-2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes. Int J Cancer 78:202

    Article  PubMed  CAS  Google Scholar 

  52. Kuhns JJ, Batalia MA, Shuqin Y, Collins EJ (1999) Poor binding of a HER-2/neu epitope (GP2) to HLA-A2.1 is dues to a lack of interaction with the center of the peptide. J Biol Chem 274:26422

    Article  Google Scholar 

  53. Bohlen P, Hicklin DJ (2003)Vaccination against angiogenesis-associated antigens: a novel cancer immunotherapy strategy. Curr Mol Med 3:773. Review

    Article  PubMed  Google Scholar 

  54. Liu J-Y, Wei Y, Yang L, Zhao X,, Tian L, Hou J, Niu Y, Liu F, Jiang Y, Xu B, Wy Y, Su J, Lou Y, He Q, Wen Y, Yang J, Kan B, Mao Y, Luo F, Peng F (2003) Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2. Blood 102:1815

    Article  PubMed  CAS  Google Scholar 

  55. Lustgarten L, Dominguez AL, Guadros C (2004) The CD8+ T cell repertoire against HER-2/neu antigens in new transgenic mice is of low avidity with antitumor activity. Eur J Immunol 34:752

    Article  PubMed  CAS  Google Scholar 

  56. Lustgarten J, Theobald M, Labadie C, LaFace D, Peterson P, Disis ML, Cheever MA, Sherman LA (1997) Identification of HER-2/neu CTL epitopes using double transgenic mice expressing HLA-A2.1 and human CD8. Hum Immunol52:109

    Article  PubMed  CAS  Google Scholar 

  57. Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin Al, Monsarrat B, Van Veithove R, Cerottini JC, Boon T, Gairin JE, Van den Eynde BJ (2000) Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity 12:107

    Article  PubMed  CAS  Google Scholar 

  58. Morgan DK, Kreuwell HT, Fleck S, Levitsky HI, Pardoll DM, Sherman LA(1998) Activation of low avidity CTL specific for a self epitope results in tumor rejection but not autoimmunity. J Immunol 160:643

    PubMed  CAS  Google Scholar 

  59. Moriai R, Asanuma K, Kobayashi D, Yajima T, Yagihashi A, Yamada M, Watanabe N. Quantitative analysis of this anti-apoptotic gene survivin-expression in malignant haematopoietic cells. Anticancer Res 21:595

  60. Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P (1988) Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54:104

    Article  Google Scholar 

  61. Mullins DW, Bullock TN, Colella TA, Robila VV, Engelhard VH (2001) Immune responses to the HLA-A*0201-restricted epitopes of tyrosinase and glycoprotein 100 enable control of melanoma outgrowth in HLA-A*0201- transgenic mice. J Immunol 167:4853

    PubMed  CAS  Google Scholar 

  62. Murray JL, Przepiorka D, Ioannides C (2000) Clinical trials of HER-2/neu-specific vaccines. Semin Oncol 27:71

    PubMed  CAS  Google Scholar 

  63. Nakamura TM, Morin GH, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB, Cech TR (1997) Science 277:955

    Article  PubMed  CAS  Google Scholar 

  64. Niethammer AG, Xiang R, Becker JC, Wodrsch H, Derte U, Karsten G, Eliceiri BP, Reisfeld RA (2002) A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med 8:1369

    Article  PubMed  CAS  Google Scholar 

  65. Overwijk WW, Tsung A, Irvine KR, Parkhurst MR, Goletz TJ, Tsung K, Carroll MW, Liu C, Moss B, Rosenberg SA, Restifo NP (1998) gp100/pmel 17 is a murine tumor rejection antigen: induction of “self”-reactive, tumoricidal T cells using high-affinity, altered peptide ligand. J Exp Med 188:277

    Article  PubMed  CAS  Google Scholar 

  66. Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Redmond C, Schlessinger J, Lippman ME, King CR (1990) Pathologic findings from the National Surgical Adjuvant Breast and Bowell Project:prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8:103

    PubMed  CAS  Google Scholar 

  67. Parker KC, Bednarek MA, Coligan JE (1994) Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol 152:163

    PubMed  CAS  Google Scholar 

  68. Parkhurst MR, Riley JP, Igarashi T, Li Y, Robbins PF, Rosenberg SA (2004) Immunization of patients with hTERT: 540-548 peptide induces peptide-reactive T lymphocytes that do not recognize tumors endogenously expressing tolemerase. Clin Cancer Res 15:4688

    Article  Google Scholar 

  69. Peiper M, Goedegebuure MP, Linehan DC, Ganguly E, Douville CC, Eberlein TJ (1997) The HER-2/neu-derived peptide p654-662 is a tumor-associated antigen in human pancreatic cancer recognized by cytotoxic T lymphocytes. Eur J Immunol 27:1115

    PubMed  CAS  Google Scholar 

  70. Perez SA, Sotiropoulou PA, Sotiriadou NM, Mamalaki A, Gritzapis AD, Echner H, Voelter W, Pawelec G, Papamichail M, Baxevanis CN (2002) HER-2/neu-derived peptide 884-899 is expressed by human breast, colorectal and pancreatic adenocarcinomas and is recognized by in-vitro-induced specific CD4+ T cell clones. Cancer Immunol Immunother 50:615

    Article  PubMed  CAS  Google Scholar 

  71. Plum SM, Fogmer WE (2004) Anti-angiogenic vaccines as a treatment modality for cancer. Curr Opin Investig Drugs 5:1243

    PubMed  CAS  Google Scholar 

  72. Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50:213

    Article  PubMed  CAS  Google Scholar 

  73. Reisfeld RA, Niethammer AG, Luo Y, Xiang R (2004) DNA vaccines suppress tumor growth and metastases by the induction of anti-angiogenesis. Immunol Rev 199:181

    Article  PubMed  CAS  Google Scholar 

  74. Reker S, Meier A, Holten-Andersen L, Svane IM, Becker JC, thor Straten P, Andersein MH (2004) Identification of novel survirin-derived CTL epitopes. Cancer Biol Ther 3:173

    PubMed  CAS  Google Scholar 

  75. Ridge JP, Di Rosa F, Matzinger P (1998) A conditioned dendritic cell can be temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393:474

    Article  PubMed  CAS  Google Scholar 

  76. Rivoltini L, Squarcina P, Loftus DJ, Castelli C, Tarsini P, Mazzocchi A, Rini F, Viggiano V, Belli F, Parmiani G (1999) A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy. Cancer Res 39:301

    Google Scholar 

  77. Rongcun Y, Salazar-Onfray F, Charo J, Malmberg KJ, Evrin K, Maes H, Komo K, Hising C, Petersson M, Larsson O, Lan L, Appella E, Sette A, Celis E, Kiessling R (1999) Identification of new HER-2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas. J Immunol 163:1037

    PubMed  CAS  Google Scholar 

  78. Ruppert J, Sidney J, Celis E, Kubo RT, Grey HM, Sette A (1993) Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules.Cell 74:929

    Article  PubMed  CAS  Google Scholar 

  79. Salazar E, Zaremba S, Arlen PM, Tsang KY, Schlom J (2000) Agonist peptide from a cytotoxic T-lymphocyte epitope of human carcinoembryonic antigen stimulates production of TC1-type cytokines and increases tyrosine phosphorylation more efficiently than cognate peptide. Int J Cancer 85:829

    Article  PubMed  CAS  Google Scholar 

  80. Sanchez-Garcia L, Grutz G (1995) Tumorigenic activity of the BCR-ABL oncogenes is mediated by BCL2. Proc Natl Acad Sci USA 92:5287

    PubMed  CAS  Google Scholar 

  81. Scardino A, Alves P, Gross DA, Tourdot S, Graff-Dubois S, Angevin E, Firat H, Chouaib S, Lemonnier F, Nadler LM, Cardoso AA, Kosmatopoulos K (2001)Identification of HER-2/neu immunogenic epitopes presented by renal cell carcinoma and other human epithelial tumors. Eur J Immunol 31:3261

    Article  PubMed  CAS  Google Scholar 

  82. Scardino A, Gross D-A, Alves P, Schultze JL, Graff-Dubois S, Faure O, Tourdot S, Chouaib S, Nadler LM, Lemonnier FA, Vonderheide RH, Cardoso AA, Kospatopoulos K (2002) HER-2/neu and hTERT cryptic epitopes as novel targets for broad spectrum tumor immunotherapy. J Immunol 168:5900

    PubMed  CAS  Google Scholar 

  83. Schoenberger PS, Toes RE, van der Voort EI, Offringa R, Melief CJM (1998) T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393:480

    Article  PubMed  CAS  Google Scholar 

  84. Sercarz EE (2000) Driver clones and determinant spreading. J Autoimmun 14:275

    Article  PubMed  CAS  Google Scholar 

  85. Sercarz EE, Lehmann PV, Ametani A, Benichou G, Miller A, Moudgil K (1993) Dominance and crypticity of T-cell antigenic determinants. Ann Rev Immunol 11:729

    Article  CAS  Google Scholar 

  86. Serody JS, Collins EJ, Tisch RM, Kuhns JJ, Freilinger JA (2000) T cell activity after dendritic cell vaccination is dependent on both the type of antigen and the mode of delivery. J Immunol 164:4961

    PubMed  CAS  Google Scholar 

  87. Shiku H, Wang L, Ikuta Y, Okugawa T, Schmitt M, Gu X, Akiyoshi K, Sunamoto J, Nakamura H (2000) Development of a cancer vaccine: peptides, proteins and DNA. Cancer Chemother Pharmacol 46:77

    Article  Google Scholar 

  88. Sidney J, Southwood S, del Guercio MF, Grey HM, Chesnut RW, Kubo RT, Sette A (1996) Specificity and degenerary in peptide binding to HLA-B7-like class I molecules. J Immunol 157:3480

    PubMed  CAS  Google Scholar 

  89. Slansky JE, Rattis FM, Boyd IF, Fahmy T, Jaffee EM, Schneck JP, Margulles DH, Pardoll DM (2000) Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC-peptide-TCR complex. Immunity 13:529

    Article  PubMed  CAS  Google Scholar 

  90. Smith SD, Wheeler MA, Plescia J, Colberg JW, Weiss RM, Altieri DC (2001) Urine detection of survirin and diagnosis of bladder cancer. J Am Med Assoc 285:324

    Article  CAS  Google Scholar 

  91. Sotiriadou R, Perez SA, Gritzapis AD, Sotiropoulou PA, Echner H, Heinzel S, Mamalaki A, Pawelec G, Voelter W, Baxevanis CN, Papamichail M (2001) Peptide HER2 (776-788) represents a naturally processed broad MHC class II-restricted T cell epitope. Br J Cancer 85:1527

    Article  PubMed  CAS  Google Scholar 

  92. Sotiropoulou PA, Perez SA, Hliopoulou EG, Missitzis I, Voelter W, Echner H, Baxevanis CN, Papamichail M (2003) Cytotoxic T-cell precursor frequencies to HER-2 (369-377) in patients with HER-2/neu-positive epithelial tumors. Br J Cancer 80:1055

    Article  CAS  Google Scholar 

  93. Sotiropoulou PA, Perez SA, Voelter W, Echner H, Missitzis I, Tsavaris NB, Papamichail M, Baxevanis CN (2003) Natural CD8+ T cell responses against MHC class I epitopes of the HER-2/neu oncoprotein in patients with epithelial tumors. Cancer Immunol Immunother 52:771

    Article  PubMed  CAS  Google Scholar 

  94. Tajima K, Ito Y, Demachi A, Nishida K, Akatsuka Y, Tsujimura K, Hida T, Morishima Y, Kuwano H, Mitsudomi T, Takahashi T, Kuzushima K (2004) Interferon-gamma differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes. Int J Cancer 20:403

    Article  CAS  Google Scholar 

  95. Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N (2000) Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 6:127

    PubMed  CAS  Google Scholar 

  96. Titu LV, Loveday RL, Maden LA, Cawkwell L, Monson JR, Greenman J (2004) Cytotoxic T-cell immunity against telomerase reverse transcriptase in colorectal cancer patients. Oncol Rep 12:871

    PubMed  CAS  Google Scholar 

  97. Thomas DG, Giordano TJ, Sanders D, Biermann S, Sondak UK, Trent JC, Pollock RE, Baker L (2005) Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma. Cancer 103:830

    Article  PubMed  CAS  Google Scholar 

  98. Tsai V, Southwood S, Sidney J, Sakaguchi K, Kawakami Y, Appella E, Sette A, Celis E (1997) Identification of subdominant CTL epitopes of the gp100 melanoma-associated tumor antigen by primary in vitro immunization with peptide-pulsed dendritic cells. J Immunol 158:1796

    PubMed  CAS  Google Scholar 

  99. Tuttle TM, Anderson BW, Thompson WE, Lee JE, Sahin A, Smith Tl, Grabstein KH, Wharton T, Ioannides CG, Murray JL (1998) Proliferative and cytokine reponses to class II HER-2/neu-associated peptides in breast cancer. Clin Cancer Res 4:2015

    PubMed  CAS  Google Scholar 

  100. Valmori D, Levy F, Miconnet I, Zajac P, Spagnoli GC, Rimold D, Lienard D, Cerrundolo J, Cerrotini C, Romero P (2000) Induction of potent antitumor CTL responses by recombinant vaccinia encoding a Melan-peptide analogue. J Immunol 164:1125

    PubMed  CAS  Google Scholar 

  101. Vertuani S, Sette A, Sidney J, Southwood S, Fikes J, Keogh E, Lindencrona JA, Ishioka G, Levitskaya J, Kiessling R (2004) Improved immunogenicity of an immunodominant epitope of the HER-2/neu protooncogene by alterations of MHC contact residues. J Immunol 172:3501

    PubMed  CAS  Google Scholar 

  102. Watson MB, Bahia H, Ashman JN, Berrieman HK, Drew P, Lind MJ, Greenman J, Cawkwell L (2004) Chromosomal alterations in breast cancer revealed by multicolour fluorescence in situ hybridization. Int J Oncol 25:277

    PubMed  CAS  Google Scholar 

  103. Wang RF (1999) Human tumor antigens: implications for cancer vaccine development. J Mol Med 77:640

    Article  PubMed  CAS  Google Scholar 

  104. Wei YQ, Huang MJ, Yang L, Zhao X, Thian L, Lu Y, Shu JM, Lu CJ, Niu T, Kang B, Mao YQ et al (2001) Immunogene therapy of tumours with vaccine based on xenopus homologous vascular endothelial growth factor as a model antigen. Proc Natl Acad Sci USA 98:11545

    Article  PubMed  CAS  Google Scholar 

  105. Williams NS, Gaynor RB, Scoggin S, Verna U, Gokaslan T, Simmang C, Flemming J, Tavana D, Frenkel E, Becerra C (2003) Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference. Clin Cancer Res 9:931

    PubMed  CAS  Google Scholar 

  106. Worley BS, van den Broeke IT, Goletz TJ, Pendleton CD, Daschbach EM, Thomas EK, Marincola FM, Helman LJ, Berzolsky JA (2001) Antigenicity of fusion proteins from sarcoma-associated chromosomal translocations. Cancer Res 61:6868

    PubMed  CAS  Google Scholar 

  107. Yi H, Fujimura Y, Ouchida M, Prasad DD, Rao VN, Reddy ES (1997) Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias. Oncogene 14:1259

    Article  PubMed  CAS  Google Scholar 

  108. Yoshimura A, Shiku H, Nakayama E (1993) Rejection of an IA+ variant line of FBL-3 leukemia by cytotoxic T lymphocytes with CD4+ and CD4− CD8+ T cell receptor-αβ phenotypes generated in CD8-depleted C57BL/6 mice. J Immunol 150:4900

    PubMed  CAS  Google Scholar 

  109. Zaks TZ, Rosenberg SA (1998) Immunization with a peptide epitope (p369-377) from HER-2/neu leads to peptide-specific cytotoxic T lymphocytes that fail to recognize HER-2/neu+ tumors. Cancer Res 58:4902

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We wish to thank Miss Joanna Doukoumopoulou for her excellent secretarial assistance

Author information

Authors and Affiliations

  1. Cancer Immunology and Immunotherapy Center, St. Savas Hospital, 171 Alexandras Ave, 11522, Athens, Greece

    Constantin N. Baxevanis, Nectaria N. Sotiriadou, Angelos D. Gritzapis, Panagiota A. Sotiropoulou, Sonia A. Perez, Nike T. Cacoullos & Michael Papamichail

Authors
  1. Constantin N. Baxevanis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nectaria N. Sotiriadou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angelos D. Gritzapis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Panagiota A. Sotiropoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sonia A. Perez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nike T. Cacoullos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael Papamichail
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Constantin N. Baxevanis.

Additional information

This article is a symposium paper from the conference “Progress in Vaccination against Cancer 2004 (PIVAC 4)”, held in Freudenstadt-Lauterbad, Black Forest, Germany, on 22–25 September 2004

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baxevanis, C.N., Sotiriadou, N.N., Gritzapis, A.D. et al. Immunogenic HER-2/neu peptides as tumor vaccines. Cancer Immunol Immunother 55, 85–95 (2006). https://doi.org/10.1007/s00262-005-0692-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-005-0692-3

Keywords

Search

Navigation