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  • Poster presentation
  • Open Access

Identification of a novel epitope derived from the cancer-germline antigen, HAGE, displaying both in-vitro and in-vivo immunogenicity

  • 1Email author,
  • 2,
  • 1,
  • 2 and
  • 1
Cancer Cell International20044 (Suppl 1) :S50

https://doi.org/10.1186/1475-2867-4-S1-S50

  • Received: 28 April 2004
  • Published:

Keywords

  • Tumour Antigen
  • Acute Myeloid Leukaemia
  • Immunogenic Peptide
  • Current Tumour
  • Specific Cytotoxicity

It is now well established that both CD4+ and CD8+ tumour-specific T-lymphocytes play critical roles in anti-tumour immunity; thus there is a desirability to identify both MHC class I and II-restricted tumour antigens that induce immunogenic responses in both in-vitro models and more significantly in an in-vivo environment. Many current tumour antigens that are potential targets fall into the category of cancer-germline (CG) antigens, and are considered to represent good candidate antigens for tumour immunotherapy based on their lack of expression on normal somatic tissues. HAGE is a novel CG gene expressed in a wide range of solid tumour tissue (eg. around 20% of melanomas, one-third of lung cancers) but also in haematological malignancies (in >50% and >20% of chronic and acute myeloid leukaemias, respectively). Here we describe the use of a combination of computer algorithms to identify potentially immunogenic peptides from the HAGE protein based on both predicted HLA affinity and proteosomal cleavage sites. An HLA-A2-binding motif contained within a longer HLA-DR-binding sequence was identified. Two peptides representing either the class I motif alone, or a longer peptide containing the class I motif within the class II motif, were then screened in in-vitro T cell sensitisation experiments using PBMC or monocyte-derived dendritic cells from healthy donors or CML patients; the class I peptide was also used in-vivo to vaccinate HLA-A2-transfected mice. We demonstrate that both these peptides are immunogenic in-vitro not only for T cells from healthy donors, but also from CML patients, as assessed by functional assays such as cytokine secretion and cytotoxicity. Moreover, immunogenicity was confirmed by using MHC/peptide tetramers to show specific expansion of sensitised T-cells. Furthermore, the class I peptide also demonstrates immuno-genicity in-vivo following vaccination of HLA-A2-transfected mice. Spleen cells isolated from these mice showed specific cytotoxicity ex-vivo. We conclude that the HLA-DR-binding peptide and the HLA-A2 motif contained therein may represent potential vaccines for the immunotherapeutic treatment of cancer, particularly CML, targeting the HAGE expression of a high proportion of tumours.

Authors’ Affiliations

(1)
Section for Transplantation Immunology and Immunohaematology, Universitätsklinikum Tübingen, ZMF, Waldhörnlestr.22, D-72072 Tübingen, Germany
(2)
Department of Life Science, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK

Copyright

© Author(s); licensee BioMed Central Ltd. 2004

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