Skip to main content
Top
Published in: Breast Cancer Research 6/2001

01-12-2001 | Review

Update on HER-2 as a target for cancer therapy: HER2/neu peptides as tumour vaccines for T cell recognition

Authors: Isabel Correa, Tim Plunkett

Published in: Breast Cancer Research | Issue 6/2001

Login to get access

Abstract

During the past decade there has been renewed interest in the use of vaccine immunotherapy for the treatment of cancer. This review focuses on HER2/neu, a tumour-associated antigen that is overexpressed in 10–40% of breast cancers and other carcinomata. Several immunogenic HER2/neu peptides recognized by T lymphocytes have been identified to be included in cancer vaccines. Some of these peptides have been assessed in clinical trials of patients with breast and ovarian cancer. Although it has been possible to detect immunological responses against the peptides in the immunized patients, no clinical responses have so far been described. Immunological tolerance to self-antigens like HER2/neu may limit the functional immune responses against them. It will be of interest to determine whether immune responses against HER2/neu epitopes can be of relevance to cancer treatment.
Literature
1.
go back to reference Miles DW: Update on herceptin in the clinical setting. Breast Cancer Res. 2001. Miles DW: Update on herceptin in the clinical setting. Breast Cancer Res. 2001.
2.
3.
go back to reference Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH: Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med. 2000, 6: 322-326. Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH: Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med. 2000, 6: 322-326.
4.
go back to reference Rosenberg SA: Progress in human tumour immunology and immunotherapy. Nature. 2001, 411: 380-384. 10.1038/35077246.CrossRefPubMed Rosenberg SA: Progress in human tumour immunology and immunotherapy. Nature. 2001, 411: 380-384. 10.1038/35077246.CrossRefPubMed
5.
go back to reference Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin AL, Monsarrat B, Van Velthove R, Cerottini JC, Boon T, Gairin JE, Van den Eynde BJ: Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity. 2000, 12: 107-117.CrossRefPubMed Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin AL, Monsarrat B, Van Velthove R, Cerottini JC, Boon T, Gairin JE, Van den Eynde BJ: Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity. 2000, 12: 107-117.CrossRefPubMed
6.
go back to reference Zaks TZ, Rosenberg SA: Immunization with a peptide epitope (p369-377) from HER-2/neu leads to peptide-specific cyto-toxic T lymphocytes that fail to recognize HER-2/neu+ tumors. Cancer Res. 1998, 58: 4902-4908.PubMed Zaks TZ, Rosenberg SA: Immunization with a peptide epitope (p369-377) from HER-2/neu leads to peptide-specific cyto-toxic T lymphocytes that fail to recognize HER-2/neu+ tumors. Cancer Res. 1998, 58: 4902-4908.PubMed
7.
go back to reference Fisk B, Blevins TL, Wharton JT, Ioannides CG: Identification of an immunodominant peptide of HER-2/neu protooncogen recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J Exp Med. 1995, 181: 2109-2117.CrossRefPubMed Fisk B, Blevins TL, Wharton JT, Ioannides CG: Identification of an immunodominant peptide of HER-2/neu protooncogen recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J Exp Med. 1995, 181: 2109-2117.CrossRefPubMed
8.
go back to reference Kobayashi H, Wood M, Song Y, Apella E, Celis E: Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. Cancer Res. 2000, 60: 5228-5236.PubMed Kobayashi H, Wood M, Song Y, Apella E, Celis E: Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. Cancer Res. 2000, 60: 5228-5236.PubMed
10.
go back to reference Zeh HJ, Perry-Lalley D, Dudley ME, Rosenberg SA, Yang JC: High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy. J Immunol. 1999, 162: 989-994.PubMed Zeh HJ, Perry-Lalley D, Dudley ME, Rosenberg SA, Yang JC: High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy. J Immunol. 1999, 162: 989-994.PubMed
11.
go back to reference Viner NJ, Nelson CA, Deck B, Unanue ER: Complexes generated by the binding of free peptides to class II MHC molecules are antigenically diverse compared with those generated by intracellular processing. J Immunol. 1996, 156: 2365-2368.PubMed Viner NJ, Nelson CA, Deck B, Unanue ER: Complexes generated by the binding of free peptides to class II MHC molecules are antigenically diverse compared with those generated by intracellular processing. J Immunol. 1996, 156: 2365-2368.PubMed
12.
go back to reference Murray JL, Przepiorka D, Ioannides C: Clinical trials of HER-2/neu-specific vaccines. Semin Oncol. 2000, 27(suppl 11): 71-75.PubMed Murray JL, Przepiorka D, Ioannides C: Clinical trials of HER-2/neu-specific vaccines. Semin Oncol. 2000, 27(suppl 11): 71-75.PubMed
13.
go back to reference Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W: Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood. 2000, 96: 3102-3108.PubMed Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W: Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood. 2000, 96: 3102-3108.PubMed
14.
go back to reference Disis ML, Grabstein KH, Sleath PR, Cheever MA: 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. 1999, 5: 1289-1297.PubMed Disis ML, Grabstein KH, Sleath PR, Cheever MA: 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. 1999, 5: 1289-1297.PubMed
15.
go back to reference Knutson KL, Schiffman K, Disis ML: Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity. J Clin Invest. 2001, 107: 477-484.CrossRefPubMedPubMedCentral Knutson KL, Schiffman K, Disis ML: Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity. J Clin Invest. 2001, 107: 477-484.CrossRefPubMedPubMedCentral
16.
go back to reference Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola F, Topalian SL, Restifo NP, Sznol M, Schwarz SL, Spiess PJ, Wunderlich JR, Seipp CA, Einhorn JH, Rogers-Freezer L, White D: Impact of cytokine administration on the generation of anti-tumor reactivity in patients with metastatic melanoma receiving a peptide vaccine. J Immunol. 1999, 163: 1690-1695.PubMedPubMedCentral Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola F, Topalian SL, Restifo NP, Sznol M, Schwarz SL, Spiess PJ, Wunderlich JR, Seipp CA, Einhorn JH, Rogers-Freezer L, White D: Impact of cytokine administration on the generation of anti-tumor reactivity in patients with metastatic melanoma receiving a peptide vaccine. J Immunol. 1999, 163: 1690-1695.PubMedPubMedCentral
17.
go back to reference Marchant M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier M, Rankin E, Parmiani G, Arienti F, Humblet Y, Boulond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van den Bruggen P, Boon T: Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer. 1999, 80: 219-230. 10.1002/(SICI)1097-0215(19990118)80:2<219::AID-IJC10>3.3.CO;2-J. Marchant M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier M, Rankin E, Parmiani G, Arienti F, Humblet Y, Boulond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van den Bruggen P, Boon T: Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer. 1999, 80: 219-230. 10.1002/(SICI)1097-0215(19990118)80:2<219::AID-IJC10>3.3.CO;2-J.
18.
go back to reference Garrido F, Ruiz-Cabello F, Cabrera T, Perez-Villar JJ, Lopez-Botet M, Duggan-Keen M, Stern PL: Implications for immunosurveillance of altered HLA class I phenotypes in human tumors. Immunol Today. 1997, 18: 89-95. 10.1016/S0167-5699(96)10075-X.CrossRefPubMed Garrido F, Ruiz-Cabello F, Cabrera T, Perez-Villar JJ, Lopez-Botet M, Duggan-Keen M, Stern PL: Implications for immunosurveillance of altered HLA class I phenotypes in human tumors. Immunol Today. 1997, 18: 89-95. 10.1016/S0167-5699(96)10075-X.CrossRefPubMed
19.
go back to reference Kawashima I, Hudson SJ, Tsai V, Southwood S, Takesato K, Apella E, Sette A, Celis E: The multiepitope approach for immunotherapy for cancer: Identification of several CTL epitopes from various tumor-associated antigens expressed on solid epithelial tumors. Hum Immunol. 1998, 59: 1-14. 10.1016/S0198-8859(97)00255-3.CrossRefPubMed Kawashima I, Hudson SJ, Tsai V, Southwood S, Takesato K, Apella E, Sette A, Celis E: The multiepitope approach for immunotherapy for cancer: Identification of several CTL epitopes from various tumor-associated antigens expressed on solid epithelial tumors. Hum Immunol. 1998, 59: 1-14. 10.1016/S0198-8859(97)00255-3.CrossRefPubMed
20.
go back to reference Kono K, Rongcun Y, Charo J, Ichihara F, Celis E, Sette A, Apella E, Sekikawa T, Matsumoto Y, Kiessling R: Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes. Int J Cancer. 1998, 78: 202-208. 10.1002/(SICI)1097-0215(19981005)78:2<202::AID-IJC14>3.3.CO;2-R.CrossRefPubMed Kono K, Rongcun Y, Charo J, Ichihara F, Celis E, Sette A, Apella E, Sekikawa T, Matsumoto Y, Kiessling R: Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes. Int J Cancer. 1998, 78: 202-208. 10.1002/(SICI)1097-0215(19981005)78:2<202::AID-IJC14>3.3.CO;2-R.CrossRefPubMed
21.
go back to reference Lustgarten J, Theobald M, Labadie C, LaFace D, Peterson P, Disis ML, Cheever MA, Sherman LA: Identification of Her-2/Neu CTL epitopes using double transgenic mice expressing HLA-A2.1 and human CD8. Hum Immunol. 1997, 52: 109-118. 10.1016/S0198-8859(96)00292-3.CrossRefPubMed Lustgarten J, Theobald M, Labadie C, LaFace D, Peterson P, Disis ML, Cheever MA, Sherman LA: Identification of Her-2/Neu CTL epitopes using double transgenic mice expressing HLA-A2.1 and human CD8. Hum Immunol. 1997, 52: 109-118. 10.1016/S0198-8859(96)00292-3.CrossRefPubMed
22.
go back to reference Rongcun Y, Salazar-Onfray F, Charo J, Malmberg KJ, Evrin K, Maes H, Kono K, Hising C, Petersson M, Larsson O, Lan L, Apella E, Sette A, Celis E, Kiessling R: Identification of new HER2/ neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinoma and melanomas. J Immunol. 1999, 163: 1037-1044.PubMed Rongcun Y, Salazar-Onfray F, Charo J, Malmberg KJ, Evrin K, Maes H, Kono K, Hising C, Petersson M, Larsson O, Lan L, Apella E, Sette A, Celis E, Kiessling R: Identification of new HER2/ neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinoma and melanomas. J Immunol. 1999, 163: 1037-1044.PubMed
23.
go back to reference Yoshino I, Goedegebuure PS, Peoples GE, Parikh AS, Dimaio JM, Lyerly HK, Gazdar AF, Eberlein TJ: HER-2/neu-derived peptides are shared antigens among human non-small cell lung cancer and ovarian cancer. Cancer Res. 1994, 54: 3387-3390.PubMed Yoshino I, Goedegebuure PS, Peoples GE, Parikh AS, Dimaio JM, Lyerly HK, Gazdar AF, Eberlein TJ: HER-2/neu-derived peptides are shared antigens among human non-small cell lung cancer and ovarian cancer. Cancer Res. 1994, 54: 3387-3390.PubMed
24.
go back to reference Kawashima I, Tsai V, Southwood S, Takesako K, Sette A, Celis E: Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. Cancer Res. 1999, 59: 431-435.PubMed Kawashima I, Tsai V, Southwood S, Takesako K, Sette A, Celis E: Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. Cancer Res. 1999, 59: 431-435.PubMed
25.
go back to reference Tanaka H, Tsunoda T, Nukaya I, Sette A, Matsuda K, Umano Y, Yamaue H, Takesato K, Tanimura H: Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER2/neu: possible immunotherapy for colorectal carcinomas. Br J Cancer. 2001, 84: 94-96. 10.1054/bjoc.2000.1547.CrossRefPubMedPubMedCentral Tanaka H, Tsunoda T, Nukaya I, Sette A, Matsuda K, Umano Y, Yamaue H, Takesato K, Tanimura H: Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER2/neu: possible immunotherapy for colorectal carcinomas. Br J Cancer. 2001, 84: 94-96. 10.1054/bjoc.2000.1547.CrossRefPubMedPubMedCentral
26.
go back to reference Okugawa T, Ikuta Y, Takahashu Y, Obata H, Tanida K, Watanabe M, Imai S, Furugen R, Nagata Y, Toyoda N, Shiku H: A novel human HER2-derived peptide homologous to the mouse Kd-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals. Eur J Immunol. 2000, 30: 3338-3346. 10.1002/1521-4141(200011)30:11<3338::AID-IMMU3338>3.3.CO;2-V.CrossRefPubMed Okugawa T, Ikuta Y, Takahashu Y, Obata H, Tanida K, Watanabe M, Imai S, Furugen R, Nagata Y, Toyoda N, Shiku H: A novel human HER2-derived peptide homologous to the mouse Kd-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals. Eur J Immunol. 2000, 30: 3338-3346. 10.1002/1521-4141(200011)30:11<3338::AID-IMMU3338>3.3.CO;2-V.CrossRefPubMed
27.
go back to reference Ikuta Y, Okugawa T, Furugen R, Nagata Y, Takahashi Y, Wang L, Ikeda H, Watanabe M, Imai S, Shiku H: A HER2/neu derived peptide, a Kd-restricted murine tumor rejection antigen, induces HER2-specific HLA-A2402-restricted CD8+ cytotoxic T lymphocytes. Int J Cancer. 2000, 87: 553-558. 10.1002/1097-0215(20000815)87:4<553::AID-IJC15>3.0.CO;2-8.CrossRefPubMed Ikuta Y, Okugawa T, Furugen R, Nagata Y, Takahashi Y, Wang L, Ikeda H, Watanabe M, Imai S, Shiku H: A HER2/neu derived peptide, a Kd-restricted murine tumor rejection antigen, induces HER2-specific HLA-A2402-restricted CD8+ cytotoxic T lymphocytes. Int J Cancer. 2000, 87: 553-558. 10.1002/1097-0215(20000815)87:4<553::AID-IJC15>3.0.CO;2-8.CrossRefPubMed
Metadata
Title
Update on HER-2 as a target for cancer therapy: HER2/neu peptides as tumour vaccines for T cell recognition
Authors
Isabel Correa
Tim Plunkett
Publication date
01-12-2001
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2001
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr330

Other articles of this Issue 6/2001

Breast Cancer Research 6/2001 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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