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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 12/2007

01-12-2007 | Original Article

HAGE, a cancer/testis antigen with potential for melanoma immunotherapy: identification of several MHC class I/II HAGE-derived immunogenic peptides

Authors: Morgan G. Mathieu, Ashley J. Knights, Graham Pawelec, Catherine L. Riley, Dorothee Wernet, François A. Lemonnier, Per Thor Straten, Ludmila Mueller, Robert C. Rees, Stephanie E. B. McArdle

Published in: Cancer Immunology, Immunotherapy | Issue 12/2007

Login to get access

Abstract

There remains a need to identify novel epitopes of potential tumour target antigens for use in immunotherapy of cancer. Here, several melanoma tissues and cell lines but not normal tissues were found to overexpress the cancer-testis antigen HAGE at the mRNA and protein level. We identified a HAGE-derived 15-mer peptide containing a shorter predicted MHC class I-binding sequence within a class II-binding sequence. However, only the longer peptide was found to be both endogenously processed and immunogenic for T cells in transgenic mice in vivo, as well as for human T cells in vitro. A different class I-binding peptide, not contained within a longer class II sequence, was subsequently found to be both immunogenic and endogenously processed in transgenic mice, as was a second class II epitope. These novel HAGE-derived epitopes may contribute to the range of immunotherapeutic targets for use in cancer vaccination programs.
Literature
1.
Adams SP, Sahota SS, Mijovic A, Czepulkowski B, Padua RA, Mufti GJ, Guinn BA (2002) Frequent expression of HAGE in chronic myeloid leukemias. Leukaemia 16:2238–2242CrossRef
2.
Assudani DP, Horton RB, Mathieu MG, McArdle SE, Rees RC (2006) The role of CD4+ T cell help in cancer immunity and the formulation of novel cancer vaccines. Cancer Immunol Immunother 56:70–80PubMedCrossRef
3.
Cordin O, Banroques J, Tanner NK, Linder P (2006) The DEAD-box protein family of RNA helicases. Gene 367:17–37PubMedCrossRef
4.
Disis ML, Gralow JR, Bernhard H, Hand SL, Rubin WD, Cheever MA (1996) Peptide-based, but not whole protein, vaccines elicit immunity to HER-2/neu, oncogenic self-protein. J Immunol 156:3151–3158PubMed
5.
Dissanayake SK, Tuera N, Ostrand-Rosenberg S (2005) Presentation of endogenously synthesized MHC class II-restricted epitopes by MHC class II cancer vaccines is independent of transporter associated with Ag processing and the proteasome. J Immunol 174:1811–1819PubMed
6.
Firat H, Garcia-Pons F, Tourdot S, Pascolo S, Scardino A, Garcia Z, Michel ML, Jack RW, Jung G, Kosmatopoulos K, Mateo L, Suhrbier A, et al (1999) H-2 class I knockout, HLA-A2.1-transgenic mice: a versatile animal model for preclinical evaluation of antitumor immunotherapeutic strategies. Eur J Immunol 29:3112–3121PubMedCrossRef
7.
Knights AJ, Zaniou A, Rees RC, Pawelec G, Muller L (2002) Prediction of an HLA-DR-binding peptide derived from Wilms’ tumour 1 protein and demonstration of in vitro immunogenicity of WT1(124–138)-pulsed dendritic cells generated according to an optimised protocol. Cancer Immunol Immunother 51:271–281PubMedCrossRef
8.
Lotze MT, Rees RC (2004) Identifying biomarkers and surrogates of tumors (cancer biometrics): correlation with immunotherapies and immune cells. Cancer Immunol Immunother 53:256–261PubMedCrossRef
9.
Martelange V, De Smet C, De Plaen E, Lurquin C, Boon T (2000) Identification on a human sarcoma of two new genes with tumour-specific expression. Cancer Res 60:3848–3855PubMed
10.
Miles AK, Matharoo-Ball B, Li G, Ahmad M, Rees RC (2006) The identification of human tumour antigens: current status and future developments. Cancer Immunol Immunother 55:996–1003PubMedCrossRef
11.
Mine T, Sato Y, Noguchi M, Sasatomi T, Gouhara R, Tsuda N, Tanaka S, Shomura H, Katagiri K, Rikimaru T, Shichijo S, Kamura T, et al (2004) Humoral responses to peptides correlate with overall survival in advanced cancer patients vaccinated with peptides based on pre-existing, peptide-specific cellular responses. Clin Cancer Res 10:929–937PubMedCrossRef
12.
Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126–129PubMedCrossRef
13.
Nagel H, Laskawi R, Eiffert H, Schlott T (2003) Analysis of the tumour suppressor genes, FHIT and WT-1, and the tumour rejection genes, BAGE, GAGE-1/2, HAGE, MAGE-1, and MAGE-3, in benign and malignant neoplasms of the salivary glands. J Clin Mol Path 56:226–231CrossRef
14.
Novellino L, Castelli C, Parmiani G (2005) A listing of human tumour antigens recognized by T cells: March 2004 update. Cancer Immunol Immunother 54:187–207PubMedCrossRef
15.
Rojas JM, McArdle SE, Horton RB, Bell M, Mian S, Li G, Ali SA, Rees RC (2004) Peptide immunisation of HLA-DR-transgenic mice permits the identification of a novel HLA-DRbeta1*0101- and HLA-DRbeta1*0401-restricted epitope from p53. Cancer Immunol Immunother 54:243–253PubMedCrossRef
16.
Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Dudley ME, Schwarz SL, Spiess PJ, Wunderlich JR, Parkhurst MR, et al (1998) Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 4:321–327PubMedCrossRef
17.
Saxova P, Buus S, Brunak S, Kesmir C (2003) Predicting proteasomal cleavage sites: a comparison of available methods. Int Immunol 15:781–787PubMedCrossRef
18.
Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardisation and commentary. Cancer Immunol 4:1–15
19.
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 254:1643–1647PubMedCrossRef
20.
Wilson BJ, Bates GJ, Nicol SM, Gregory DJ, Perkins ND, Fuller-Pace FV (2004) The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner. BMC Mol Biol 6:5–11
21.
Yang L, Lin C, Liu ZR (2005) Phosphorylations of DEAD box p68 RNA helicase are associated with cancer development and cell proliferation. Mol Cancer Res 3:355–363PubMedCrossRef
22.
Yee C, Thompson JA, Roche P, Byrd DR, Lee PP, Piepkorn M, Kenyon K, Davis MM, Riddell SR, Greenberg PD (2000) Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of T-cell mediated vitiligo. J Exp Med 192:1637–1644PubMedCrossRef
Metadata
Title
HAGE, a cancer/testis antigen with potential for melanoma immunotherapy: identification of several MHC class I/II HAGE-derived immunogenic peptides
Authors
Morgan G. Mathieu
Ashley J. Knights
Graham Pawelec
Catherine L. Riley
Dorothee Wernet
François A. Lemonnier
Per Thor Straten
Ludmila Mueller
Robert C. Rees
Stephanie E. B. McArdle
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 12/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-007-0331-2

Other articles of this Issue 12/2007

Cancer Immunology, Immunotherapy 12/2007 Go to the issue

Original Article

Semi-allogeneic dendritic cells can induce antigen-specific T-cell activation, which is not enhanced by concurrent alloreactivity

Original Article

Low TCR avidity and lack of tumor cell recognition in CD8+ T cells primed with the CEA-analogue CAP1-6D peptide

Original Article

Robust anti-tumor immunity and memory in Rag-1-deficient mice following adoptive transfer of cytokine-primed splenocytes and tumor CD80 expression

Original Article

Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo

Original Article

Distinct changes of dendritic cell number and IL-12 mRNA level in adjacent mucosa throughout the colorectal adenoma–carcinoma sequence

Original Article

Spontaneous and vaccine induced AFP-specific T cell phenotypes in subjects with AFP-positive hepatocellular cancer
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