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

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 6/2007

01-06-2007 | Original Article

In the FVB/N HER-2/neu transgenic mouse both peripheral and central tolerance limit the immune response targeting HER-2/neu induced by Listeria monocytogenes-based vaccines

Authors: Reshma Singh, Yvonne Paterson

Published in: Cancer Immunology, Immunotherapy | Issue 6/2007

Login to get access

Abstract

Listeria monocytogenes-based vaccines for HER-2/neu are capable of breaking tolerance in FVB/N rat HER-2/neu transgenic mice. The growth of implanted NT-2 tumors, derived from a spontaneously occurring tumor in the FVB/N HER-2/neu transgenic mouse, was significantly slower in these mice following vaccination with a series of L. monocytogenes-based vaccines for HER-2/neu. Mechanisms of T cell tolerance that exist in these transgenic mice include the absence of functional high avidity anti-HER-2/neu CD8+ T cells and the presence of CD4+CD25+ regulatory T cells. The in vivo depletion of these regulatory T cells resulted in the slowing in growth of tumors even without the treatment of mice with an anti-HER-2/neu vaccine. The average avidities of responsive CD8+ T cells to six of the nine epitopes in HER-2/neu we examined, four of which were identified in this study, are shown here to be of a lower average avidity in the transgenic mice versus wild type FVB/N mice. In contrast, the average avidity of CD8+ T cells to three epitopes that showed the lowest avidity in the wild-type mice did not differ between wild type and transgenic mice. This study demonstrates the ability of L. monocytogenes-based vaccines to impact upon tolerance to HER-2/neu in FVB/N HER-2/neu transgenic mice and further defines some of the aspects of tolerance in these mice.
Literature
1.
2.
Chattopadhyay S, Mehrotra S, Chhabra A, Hegde U, Mukherji B, Chakraborty NG (2006) Effect of CD4+CD25+ and CD4+CD25- T regulatory cells on the generation of cytolytic T cell response to a self but human tumor-associated epitope in vitro. J Immunol 176:984PubMed
3.
Wang RF, Peng G, Wang HY (2006) Regulatory T cells and Toll-like receptors in tumor immunity. Semin Immunol 18:136PubMedCrossRef
4.
Lauritzsen GF, Hofgaard PO, Schenck K, Bogen B (1998) Clonal deletion of thymocytes as a tumor escape mechanism. Int J Cancer 78:216PubMedCrossRef
5.
De Visser KE, Schumacher TN, Kruisbeek AM (2003) CD8+ T cell tolerance and cancer immunotherapy. J Immunother 26:1PubMedCrossRef
6.
Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia M, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942PubMedCrossRef
7.
Nomura T, Sakaguchi S (2005) Naturally arising CD25+CD4+ regulatory T cells in tumor immunity. Curr Top Microbiol Immunol 293:287PubMedCrossRef
8.
Schirrmacher V, Feuerer M, Beckhove P, Ahlert T, Umansky V (2002) T cell memory, anergy and immunotherapy in breast cancer. J Mammary Gland Biol Neoplasia 7:201PubMedCrossRef
9.
Riezebos-Brilman A, Regts J, Freyschmidt EJ, Dontje B, Wilschut J, Daemen T (2005) Induction of human papilloma virus E6/E7-specific cytotoxic T-lymphocyte activity in immune-tolerant, E6/E7-transgenic mice. Gene Ther 12:1410PubMedCrossRef
10.
Esposito V, Palescandolo E, Spugnini EP, Montesarchio V, De Luca A, Cardillo I, Cortese G, Baldi A, Chirianni A (2006) Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma. Clin Cancer Res 12:2634PubMedCrossRef
11.
Knutson K, Schiffman LK, Rinn K, Disis ML (1999) Immunotherapeutic approaches for the treatment of breast cancer. J Mammary Gland Biol Neoplasia 4:353PubMedCrossRef
12.
Disis ML, Cheever MA (1997) HER-2/neu protein: a target for antigen-specific immunotherapy of human cancer. Adv Cancer Res 71:343PubMedCrossRef
13.
Coronella JA, Telleman P, Kingsbury GA, Truong TD, Hays S, Junghans RP (2001) Evidence for an antigen-driven humoral immune response in medullary ductal breast cancer. Cancer Res 61:7889PubMed
14.
Peoples GE, Smith RC, Linehan DC, Yoshino I, Goedegebuure PS, Eberlein TJ (1995) Shared T cell epitopes in epithelial tumors. Cell Immunol 164:279PubMedCrossRef
15.
Tuttle TM, Anderson BW, Thompson WE, Lee JE, Sahin A, Smith TL, Grabstein KH, Wharton JT, Ioannides CG, Murray JL (1998) Proliferative and cytokine responses to class II HER-2/neu-associated peptides in breast cancer patients. Clin Cancer Res 4:2015PubMed
16.
Lenahan C, Dennis C, Isakovich NV, Pories SE (2005) Breast cancer: what’s HER-2/neu got to do with it? Curr Surg 62:459PubMedCrossRef
17.
Muller WJ (1991) Expression of activated oncogenes in the murine mammary gland: transgenic models for human breast cancer. Cancer Metastasis Rev 10:217PubMedCrossRef
18.
Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ (1992) Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA 89:10578PubMedCrossRef
19.
Nanni P, Nicoletti G, De Giovanni C, Landuzzi L, Di Carlo E, Cavallo F, Pupa SM, Rossi I, Colombo MP, Ricci C, Astolfi A, Musiani P, Forni G, Lollini PL (2001) Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice. J Exp Med 194:1195PubMedCrossRef
20.
Cefai D, Morrison BW, Sckell A, Favre L, Balli M, Leunig M, Gimmi CD (1999) Targeting HER-2/neu for active-specific immunotherapy in a mouse model of spontaneous breast cancer. Int J Cancer 83:393PubMedCrossRef
21.
Nagata Y, Furugen R, Hiasa A, Ikeda H, Ohta N, Furukawa K, Nakamura H, Kanematsu T, Shiku H (1997) Peptides derived from a wild-type murine proto-oncogene c-erbB-2/HER2/neu can induce CTL and tumor suppression in syngeneic hosts. J Immunol 159:1336PubMed
22.
Singh R, Dominiecki ME, Jaffee EM, Paterson Y (2005) Fusion to Listeriolysin O and delivery by Listeria monocytogenes enhances the immunogenicity of HER-2/neu and reveals subdominant epitopes in the FVB/N mouse. J Immunol 175:3663PubMed
23.
Reilly RT, Gottlieb MB, Ercolini AM, Machiels JP, Kane CE, Okoye FI, Muller WJ, Dixon KH, Jaffee EM (2000) HER-2/neu is a tumor rejection target in tolerized HER-2/neu transgenic mice. Cancer Res 60:3569PubMed
24.
Gallo P, Dharmapuri S, Nuzzo M, Maldini D, Iezzi M, Cavallo F, Musiani P, Forni G, Monaci P (2005) Xenogeneic immunization in mice using HER2 DNA delivered by an adenoviral vector. Int J Cancer 113:67PubMedCrossRef
25.
Pan ZK, Ikonomidis G, Lazenby A, Pardoll D, Paterson Y (1995) A recombinant Listeria monocytogenes vaccine expressing a model tumour antigen protects mice against lethal tumour cell challenge and causes regression of established tumours. Nat Med 1:471PubMedCrossRef
26.
Gunn GR, Zubair A, Peters C, Pan ZK, Wu TC, Paterson Y (2001) Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16. J Immunol 167:6471PubMed
27.
Ercolini AM, Machiels JP, 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 tumors from HER-2/neu-transgenic mice. J Immunol 170:4273PubMed
28.
Wolpoe ME, Lutz ER, Ercolini AM, Murata S, Ivie SE, Garrett ES, Emens LA, Jaffee EM, Reilly RT (2003) HER-2/neu-specific monoclonal antibodies collaborate with HER-2/neu-targeted granulocyte macrophage colony-stimulating factor secreting whole cell vaccination to augment CD8+ T cell effector function and tumor-free survival in Her-2/neu-transgenic mice. J Immunol 171:2161PubMed
29.
Drebin JA, Link VC, Greene MI (1988) Monoclonal antibodies reactive with distinct domains of the neu oncogene-encoded p185 molecule exert synergistic anti-tumor effects in vivo. Oncogene 2:273PubMed
30.
Morgan DJ, Kreuwel 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 160:643PubMed
31.
Singh R, Paterson Y (2006) Vaccination strategy determines the emergence and dominance of CD8+ T-cell epitopes in a FVB/N rat HER-2/neu mouse model of breast cancer. Cancer Res 66:7748PubMedCrossRef
32.
Rubocki RJ, Lee DR, Lie WR, Myers NB, Hansen TH (1990) Molecular evidence that the H-2D and H-2L genes arose by duplication. Differences between the evolution of the class I genes in mice and humans. J Exp Med 171:2043PubMedCrossRef
33.
Lee DR, Rubocki RJ, Lie WR, Hansen TH (1988) The murine MHC class I genes, H-2Dq and H-2Lq, are strikingly homologous to each other, H-2Ld, and two genes reported to encode tumor-specific antigens. J Exp Med 168:1719PubMedCrossRef
34.
Kattman SJ, Lukin KR, Oh JZ, Berg RE, Staerz UD (2005) Maturational stage-dependent thymocyte responses to TCR engagement. Eur J Immunol 35:2051PubMedCrossRef
35.
Ercolini AM, Ladle BH, Manning EA, Pfannenstiel LW, Armstrong TD, Machiels JP, Bieler JG, Emens LA, Reilly RT, Jaffee EM (2005) Recruitment of latent pools of high-avidity CD8 (+) T cells to the antitumor immune response. J Exp Med 201:1591PubMedCrossRef
36.
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 54:16PubMed
37.
Disis ML, Pupa SM, Gralow JR, Dittadi R, Menard S, Cheever MA (1997) High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J Clin Oncol 15:3363PubMed
38.
Molina MA, Codony-Servat J, Albanell J, Rojo F, Arribas J, Baselga J (2001) Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res 61:4744PubMed
39.
Hurley J, Doliny P, Reis I, Silva O, Gomez-Fernandez C, Velez P, Pauletti G, Pegram MD, Slamon DJ (2006) Docetaxel, Cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol 24:1831PubMedCrossRef
40.
Drebin JA, Link VC, Greene MI (1988) Monoclonal antibodies specific for the neu oncogene product directly mediate anti-tumor effects in vivo. Oncogene 2:387PubMed
41.
Ambrosino E, Spadaro M, Iezzi M, Curcio C, Forni G, Musiani P, Wei WZ, Cavallo F (2006) Immunosurveillance of Erbb2 carcinogenesis in transgenic mice is concealed by a dominant regulatory T-cell self-tolerance. Cancer Res 66:7734PubMedCrossRef
42.
Hussain SF, Paterson Y (2004) CD4+CD25+ regulatory T cells that secrete TGFbeta and IL-10 are preferentially induced by a vaccine vector. J Immunother 27:339PubMedCrossRef
43.
Lustgarten J, Dominguez AL, Cuadros C (2004) The CD8+ T cell repertoire against Her-2/neu antigens in neu transgenic mice is of low avidity with antitumor activity. Eur J Immunol 34:752PubMedCrossRef
44.
Li W, Berencsi K, Basak S, Somasundaram R, Ricciardi RP, Gonczol E, Zaloudik J, Linnenbach A, Maruyama H, Miniou P, Herlyn D (1997) Human colorectal cancer (CRC) antigen CO17-1A/GA733 encoded by adenovirus inhibits growth of established CRC cells in mice. J Immunol 159:763PubMed
45.
Lo Iacono M, Cavallo F, Quaglino E, Rolla S, Iezzi M, Pupa SM, De Giovanni C, Lollini PL, Musiani P, Forni G, Calogero RA (2005) A limited autoimmunity to p185neu elicited by DNA and allogeneic cell vaccine hampers the progression of preneoplastic lesions in HER-2/NEU transgenic mice. Int J Immunopathol Pharmacol 18:351PubMed
46.
Ramanathan RK, Lee KM, McKolanis J, Hitbold E, Schraut W, Moser AJ, Warnick E, Whiteside T, Osborne J, Kim H, Day R, Troetschel M, Finn OJ (2005) Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Cancer Immunol Immunother 54:254PubMedCrossRef
47.
Zbar AP, Thomas H, Wilkinson RW, Wadhwa M, Syrigos KN, Ross EL, Dilger P, Allen-Mersh TG, Kmiot WA, Epenetos AA, Snary D, Bodmer WF (2005) Immune responses in advanced colorectal cancer following repeated intradermal vaccination with the anti-CEA murine monoclonal antibody, PR1A3: results of a phase I study. Int J Colorectal Dis 20:403PubMedCrossRef
48.
Lustgarten J, Dominguez AL, Pinilla C (2006) Identification of cross-reactive peptides using combinatorial libraries circumvents tolerance against Her-2/neu-immunodominant epitope. J Immunol 176:1796PubMed
49.
Duraiswamy J, Bharadwaj M, Tellam J, Connolly G, Cooper L, Moss D, Thomson S, Yotnda P, Khanna R (2004) Induction of therapeutic T-cell responses to subdominant tumor-associated viral oncogene after immunization with replication-incompetent polyepitope adenovirus vaccine. Cancer Res 64:1483PubMedCrossRef
50.
Slansky JE, Rattis FM, Boyd LF, Fahmy T, Jaffee EM, Schneck JP, Margulies DH, Pardoll DM (2000) Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC–peptide–TCR complex. Immunity 13:529PubMedCrossRef
51.
Tumenjargal S, Gellrich S, Linnemann T, Muche JM, Lukowsky A, Audring H, Wiesmuller KH, Sterry W, Walden P (2003) Anti-tumor immune responses and tumor regression induced with mimotopes of a tumor-associated T cell epitope. Eur J Immunol 33:3175PubMedCrossRef
52.
Luo W, Ko E, Hsu JC, Wang X, Ferrone S (2006) Targeting melanoma cells with human high molecular weight-melanoma associated antigen-specific antibodies elicited by a peptide mimotope: functional effects. J Immunol 176:6046PubMed
Metadata
Title
In the FVB/N HER-2/neu transgenic mouse both peripheral and central tolerance limit the immune response targeting HER-2/neu induced by Listeria monocytogenes-based vaccines
Authors
Reshma Singh
Yvonne Paterson
Publication date
01-06-2007
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 6/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0237-4

Other articles of this Issue 6/2007

Cancer Immunology, Immunotherapy 6/2007 Go to the issue

Meeting Report

Cellular therapy of cancer symposium December 2nd–3rd 2006 Manchester, UK

Original Article

Increased blood spermine levels decrease the cytotoxic activity of lymphokine-activated killer cells: a novel mechanism of cancer evasion

Original Article

Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2

Original Article

Immunoscreening of a cutaneous T-cell lymphoma library for plasma membrane proteins

Original Article

A new tumor-specific antigen encoded by MAGE-C2 and presented to cytolytic T lymphocytes by HLA-B44

Original Article

Immunization of Rhesus monkeys with a SialylTn–mAb17-1A conjugate vaccine co-formulated with QS-21 induces a temporary systemic cytokine release and NK cytotoxicity against tumor cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

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