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Published in: Breast Cancer Research 2/2001

01-04-2001 | Commentary

Challenges to the development of antigen-specific breast cancer vaccines

Authors: Matthew J Scanlan, Dirk Jäger

Published in: Breast Cancer Research | Issue 2/2001

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Abstract

Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape.
Literature
1.
go back to reference van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T: A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991, 254: 1643-1647.CrossRefPubMed van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T: A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991, 254: 1643-1647.CrossRefPubMed
2.
go back to reference Sahin U, Türeci Ö, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M: Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA. 1995, 92: 11810-11813.CrossRefPubMedPubMedCentral Sahin U, Türeci Ö, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M: Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA. 1995, 92: 11810-11813.CrossRefPubMedPubMedCentral
3.
go back to reference Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD: Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA. 1998, 95: 7556-7561. 10.1073/pnas.95.13.7556.CrossRefPubMedPubMedCentral Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD: Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA. 1998, 95: 7556-7561. 10.1073/pnas.95.13.7556.CrossRefPubMedPubMedCentral
4.
go back to reference Wang RF, Wang X, Atwood AC, Topalian SL, Rosenberg SA: Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumor antigen. Science. 1999, 284: 1351-1354. 10.1126/science.284.5418.1351.CrossRefPubMed Wang RF, Wang X, Atwood AC, Topalian SL, Rosenberg SA: Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumor antigen. Science. 1999, 284: 1351-1354. 10.1126/science.284.5418.1351.CrossRefPubMed
5.
go back to reference Hodge JW: Carcinoembryonic antigen as a target for cancer vaccines. Cancer Immunol Immunother. 1996, 43: 127-134. 10.1007/s002620050313.CrossRefPubMed Hodge JW: Carcinoembryonic antigen as a target for cancer vaccines. Cancer Immunol Immunother. 1996, 43: 127-134. 10.1007/s002620050313.CrossRefPubMed
6.
go back to reference Morse MA, Deng Y, Coleman D, Hull S, Kitrell-Fisher E, Nair S, Schlom J, Ryback ME, Lyerly HK: A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin Cancer Res. 1999, 5: 1331-1338.PubMed Morse MA, Deng Y, Coleman D, Hull S, Kitrell-Fisher E, Nair S, Schlom J, Ryback ME, Lyerly HK: A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin Cancer Res. 1999, 5: 1331-1338.PubMed
7.
go back to reference Van den Eynde BJ, van der Bruggen P: T cell defined tumor antigens. Curr Opin Immunol. 1997, 9: 684-693. 10.1016/S0952-7915(97)80050-7.CrossRefPubMed Van den Eynde BJ, van der Bruggen P: T cell defined tumor antigens. Curr Opin Immunol. 1997, 9: 684-693. 10.1016/S0952-7915(97)80050-7.CrossRefPubMed
8.
go back to reference Chen YT, Scanlan MJ, Obata Y, Old LJ: Identification of human tumor antigens by serological expression cloning. In Principles and Practice of Biologic Therapy of Cancer. Edited by Rosenberg SA. Philadelphia PA: Lippincott Williams & Wilkins,. 2000, 557-570. Chen YT, Scanlan MJ, Obata Y, Old LJ: Identification of human tumor antigens by serological expression cloning. In Principles and Practice of Biologic Therapy of Cancer. Edited by Rosenberg SA. Philadelphia PA: Lippincott Williams & Wilkins,. 2000, 557-570.
9.
go back to reference Jäger E, Gnjatic S, Nagata Y, Stockert E, Jäger D, Karbach J, Neumann A, Rieckenberg J, Chen YT, Ritter G, Hoffman E, Arand M, Old LJ, Knuth A: Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers. Proc Natl Acad Sci USA. 2000, 97: 12198-12203. 10.1073/pnas.220413497.CrossRefPubMedPubMedCentral Jäger E, Gnjatic S, Nagata Y, Stockert E, Jäger D, Karbach J, Neumann A, Rieckenberg J, Chen YT, Ritter G, Hoffman E, Arand M, Old LJ, Knuth A: Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers. Proc Natl Acad Sci USA. 2000, 97: 12198-12203. 10.1073/pnas.220413497.CrossRefPubMedPubMedCentral
10.
go back to reference Thurner B, Haendle I, Roder C, Dieckmann D, Keikavoussi P, Jonuleit H, Bender A, Maczek C, Schreiner D, von den Driesch P, Brocker EB, Steinman RM, Enk A, Kampgen E, Schuler G: Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med. 1999, 190: 1669-1678. 10.1084/jem.190.11.1669.CrossRefPubMedPubMedCentral Thurner B, Haendle I, Roder C, Dieckmann D, Keikavoussi P, Jonuleit H, Bender A, Maczek C, Schreiner D, von den Driesch P, Brocker EB, Steinman RM, Enk A, Kampgen E, Schuler G: Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med. 1999, 190: 1669-1678. 10.1084/jem.190.11.1669.CrossRefPubMedPubMedCentral
11.
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
12.
go back to reference Soussi T: p53 Antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000, 60: 1777-1788.PubMed Soussi T: p53 Antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000, 60: 1777-1788.PubMed
13.
go back to reference Chikamatsu K, Nakano K, Storkus WJ, Appella E, Lotze MT, Whiteside TL, DeLeo AB: Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells. Clin Cancer Res. 1999, 5: 1281-1288.PubMed Chikamatsu K, Nakano K, Storkus WJ, Appella E, Lotze MT, Whiteside TL, DeLeo AB: Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells. Clin Cancer Res. 1999, 5: 1281-1288.PubMed
14.
go back to reference Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jäger E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der 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.CrossRefPubMed Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jäger E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der 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.CrossRefPubMed
15.
go back to reference Paterson Y, Ikonomidis G: Recombinant Listeria monocytogenes cancer vaccines. Curr Opin Immunol. 1996, 8: 664-669. 10.1016/S0952-7915(96)80083-5.CrossRefPubMed Paterson Y, Ikonomidis G: Recombinant Listeria monocytogenes cancer vaccines. Curr Opin Immunol. 1996, 8: 664-669. 10.1016/S0952-7915(96)80083-5.CrossRefPubMed
17.
go back to reference Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D: Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998, 4: 328-332.CrossRefPubMed Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D: Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998, 4: 328-332.CrossRefPubMed
18.
go back to reference Murphy GP, Tjoa BA, Simmons SJ, Jarisch J, Bowes VA, Ragde H, Rogers M, Elgamal A, Kenny GM, Cobb OE, Ireton RC, Troychak MJ, Salgaller ML, Boynton AL: Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease. Prostate. 1999, 38: 73-78. 10.1002/(SICI)1097-0045(19990101)38:1<73::AID-PROS9>3.3.CO;2-M.CrossRefPubMed Murphy GP, Tjoa BA, Simmons SJ, Jarisch J, Bowes VA, Ragde H, Rogers M, Elgamal A, Kenny GM, Cobb OE, Ireton RC, Troychak MJ, Salgaller ML, Boynton AL: Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease. Prostate. 1999, 38: 73-78. 10.1002/(SICI)1097-0045(19990101)38:1<73::AID-PROS9>3.3.CO;2-M.CrossRefPubMed
19.
go back to reference Lodge PA, Jones LA, Bader RA, Murphy GP, Salgaller ML: Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial. Cancer Res. 2000, 60: 829-833.PubMed Lodge PA, Jones LA, Bader RA, Murphy GP, Salgaller ML: Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial. Cancer Res. 2000, 60: 829-833.PubMed
20.
go back to reference Kawakami Y, Eliyahu S, Jennings C, Sakaguchi K, Kang X, Southwood S, Robbins PF, Sette A, Appella E, Rosenberg SA: Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression. J Immunol. 1995, 154: 3961-3968.PubMed Kawakami Y, Eliyahu S, Jennings C, Sakaguchi K, Kang X, Southwood S, Robbins PF, Sette A, Appella E, Rosenberg SA: Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression. J Immunol. 1995, 154: 3961-3968.PubMed
21.
22.
go back to reference Jäger E, Ringhoffer M, Karbach J, Arand M, Oesch F, Knuth A: Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses: evidence for immunoselection of antigen-loss variants in vivo. Int J Cancer. 1996, 66: 470-476. 10.1002/(SICI)1097-0215(19960516)66:4<470::AID-IJC10>3.0.CO;2-C.CrossRefPubMed Jäger E, Ringhoffer M, Karbach J, Arand M, Oesch F, Knuth A: Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses: evidence for immunoselection of antigen-loss variants in vivo. Int J Cancer. 1996, 66: 470-476. 10.1002/(SICI)1097-0215(19960516)66:4<470::AID-IJC10>3.0.CO;2-C.CrossRefPubMed
23.
go back to reference Wojtowicz-Praga S, Verma UN, Wakefield L, Esteban JM, Hartmann D, Mazumder A: Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor beta antibody and interleukin-2. J Immunother Emphasis Tumor Immunol. 1996, 19: 169-175.CrossRefPubMed Wojtowicz-Praga S, Verma UN, Wakefield L, Esteban JM, Hartmann D, Mazumder A: Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor beta antibody and interleukin-2. J Immunother Emphasis Tumor Immunol. 1996, 19: 169-175.CrossRefPubMed
24.
go back to reference Leach DR, Krummel MF, Allison JP: Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996, 271: 1734-1736.CrossRefPubMed Leach DR, Krummel MF, Allison JP: Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996, 271: 1734-1736.CrossRefPubMed
25.
go back to reference Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin AL, Monsarrat B, Van Velthoven 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 Velthoven 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
26.
go back to reference Jäger D, Stockert E, Gure AO, Scanlan MJ, Karbach J, Jäger E, Knuth A, Old LJ, Chen YT: Identification of a tissue-specific transcription factor in breast tissue by serological screening of a breast cancer library. Submitted. 2000 Jäger D, Stockert E, Gure AO, Scanlan MJ, Karbach J, Jäger E, Knuth A, Old LJ, Chen YT: Identification of a tissue-specific transcription factor in breast tissue by serological screening of a breast cancer library. Submitted. 2000
27.
go back to reference Sahin U, Tureci O, Chen YT, Seitz G, Villena-Heinsen C, Old LJ, Pfreundschuh M: Expression of multiple cancer/testis (CT) antigens in breast cancer and melanoma: basis for polyvalent CT vaccine strategies. Int J Cancer. 1998, 78: 387-389. 10.1002/(SICI)1097-0215(19981029)78:3<387::AID-IJC22>3.0.CO;2-2.CrossRefPubMed Sahin U, Tureci O, Chen YT, Seitz G, Villena-Heinsen C, Old LJ, Pfreundschuh M: Expression of multiple cancer/testis (CT) antigens in breast cancer and melanoma: basis for polyvalent CT vaccine strategies. Int J Cancer. 1998, 78: 387-389. 10.1002/(SICI)1097-0215(19981029)78:3<387::AID-IJC22>3.0.CO;2-2.CrossRefPubMed
28.
go back to reference Chen YT, Gure AO, Tsang S, Stockert E, Jager E, Knuth A, Old LJ: Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci USA. 1998, 95: 6919-6923. 10.1073/pnas.95.12.6919.CrossRefPubMedPubMedCentral Chen YT, Gure AO, Tsang S, Stockert E, Jager E, Knuth A, Old LJ: Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci USA. 1998, 95: 6919-6923. 10.1073/pnas.95.12.6919.CrossRefPubMedPubMedCentral
29.
go back to reference Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB, Moe R, Cheever MA: Existent T cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res. 1994, 54: 16-20.PubMed Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB, Moe R, Cheever MA: Existent T cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res. 1994, 54: 16-20.PubMed
30.
go back to reference Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jäger D, Chen YT, Mackay A, O'Hare MJ, Old LJ: Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. Submitted. 2000 Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jäger D, Chen YT, Mackay A, O'Hare MJ, Old LJ: Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. Submitted. 2000
31.
go back to reference Runnebaum IB, Nagarajan M, Bowman M, Soto D, Sukumar S: Mutations in p53 as potential molecular markers for human breast cancer. Proc Natl Acad Sci USA. 1991, 88: 10657-10661.CrossRefPubMedPubMedCentral Runnebaum IB, Nagarajan M, Bowman M, Soto D, Sukumar S: Mutations in p53 as potential molecular markers for human breast cancer. Proc Natl Acad Sci USA. 1991, 88: 10657-10661.CrossRefPubMedPubMedCentral
Metadata
Title
Challenges to the development of antigen-specific breast cancer vaccines
Authors
Matthew J Scanlan
Dirk Jäger
Publication date
01-04-2001
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2001
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr278

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