Article

Identification of NM23-H2 as a tumour-associated antigen in chronic myeloid leukaemia.

Department of Hematology and Internal Oncology, University of Leipzig, Leipzig, Germany.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 10.16). 06/2008; 22(8):1542-50. DOI:10.1038/leu.2008.107
Source: PubMed

ABSTRACT Therapeutic effects of haematopoietic stem cell transplantation are not limited to maximal chemoradiotherapy and subsequent bone marrow regeneration, but include specific as well as unspecific immune reactions known as graft-versus-leukaemia (GvL) effects. Specific immune reactions are likely to be particularly relevant to the long-term treatment of diseases, such as chronic myeloid leukaemia (CML), in which residual cells may remain quiescent and unresponsive to cytotoxic and molecular therapies for long periods of time. Specific GvL effects result from the expression on leukaemic cells of specific tumour-associated antigens (TAAs) in the context of HLA proteins. As human leukocyte antigen (HLA) types vary widely, the development of broadly applicable tumour vaccines will require the identification of multiple TAAs active in different HLA backgrounds. Here, we describe the identification of NM23-H2 as a novel HLA-A32-restricted TAA of CML cells and demonstrate the presence of specifically reactive T cells in a patient 5 years after transplantation. As the NM23 proteins are aberrantly expressed in a range of different tumours, our findings suggest potential applications beyond CML and provide a new avenue of investigation into the molecular mechanisms underlying CML.

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    ABSTRACT: Cancer now affects 1 in 3 people prompting an expansion in new and improved diagnostic techniques. Treatment modes include ways to boost the immune system, which is already adept at destroying infected tissues, and which may be guided to target cancerous cells. This is more commonly known as cancer immunotherapy and it has the potential to provide an effective targeted and personalised medicine for the elimination of cancer cells. We know that some specific proteins are expressed at very low levels in healthy cells but are overexpressed in cancer cells. Such differential expression can be studied in the laboratory (on the bench) and after much evidencing of their clinical utility may be used as therapy targets for cancer patients (at the bedside). To this end we describe how tumour antigens are researched in the literature (in silico) or identified and validated through broader (immuno-) screening programmes. We discuss how animal models are utilised to show the effect of targeting tumour antigens on the development of cancer. Finally we overview how the target antigen will need to stimulate the immune system in a way which best induces effective responses. This chapter overviews current practises with regards to antigen and peptide identification and the journey from bench to bedside.
    01/2013: pages 298-325;
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    [show abstract] [hide abstract]
    ABSTRACT: Cancer now affects 1 in 3 people prompting an expansion in new and improved diagnostic techniques. Treatment modes include ways to boost the immune system, which is already adept at destroying infected tissues, and which may be guided to target cancerous cells. This is more commonly known as cancer immunotherapy and it has the potential to provide an effective targeted and personalised medicine for the elimination of cancer cells. We know that some specific proteins are expressed at very low levels in healthy cells but are overexpressed in cancer cells. Such differential expression can be studied in the laboratory (on the bench) and after much evidencing of their clinical utility may be used as therapy targets for cancer patients (at the bedside). To this end we describe how tumour antigens are researched in the literature (in silico) or identified and validated through broader (immuno-) screening programmes. We discuss how animal models are utilised to show the effect of targeting tumour antigens on the development of cancer. Finally we overview how the target antigen will need to stimulate the immune system in a way which best induces effective responses. This chapter overviews current practises with regards to antigen and peptide identification and the journey from bench to bedside.
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    ABSTRACT: For solid tumors of a malignant origin, the expression of the nm23-H1 gene is a positive prognostic factor. However, for chronic myeloid leukemia (CML), the prognostic role of nm23-H1 gene expression is unknown. The present study investigated the impact of nm23-H1 gene expression on the proliferation and migration of the CML K562 cell line to elucidate the association between nm23-H1 gene expression and CML cell survival. An RNAi lipo-recombinant plasmid of the nm23-H1 gene (pGCsi-nm23-H1) was constructed and transfected into the K562 cells. RT-PCR and western blotting were used to detect nm23-H1 mRNA and protein expression, respectively. The anchorage-independent growth ability of the transfected cells was observed in soft agar culture and the ability of the K562 cells to migrate was determined using a Transwell assay. Following the successful construction and transfection of the pGCsi-nm23-H1 plasmid into the K562 cells, nm23-H1 mRNA and protein expression levels were significantly lower compared with the control group. The stably-transfected pGCsi-nm23-H1 K562 cells exhibited a markedly increased ability to form colonies and the number and sizes of the colonies were significantly increased compared with those of the control. In vitro, the cells migrated through a Matrigel-coated membrane during incubation for 20 h. The Transwell assay revealed that the quantitative number of pGCsi-nm23-H1 K562 cells that migrated into the lower compartment of the invasion chamber was markedly increased compared with the control. In conclusion, nm23-H1 gene expression may inhibit K562 cell proliferation and migration. nm23-H1 may be a cancer suppressor gene and play a significant role in inhibiting the survival of CML cells.
    Oncology letters 10/2013; 6(4):1093-1097. · 0.24 Impact Factor

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Apr 10, 2014