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The 1170 A–P single-nucleotide polymorphism (SNP) in the Her-2/neu protein (HER2) as a minor histocompatibility antigen (mHag)

Leukemia volume 23, pages 1926–1929 (2009)Cite this article

The characterization of SNP could be clinically applied, for example, by vaccination to increase the precursor frequency of specific cells in donors before the harvest of cells, or in patients subsequent to HCT. With regard to the in vivo relevance after HCT, it would be interesting to study a suitable donor–patient cohort (HLA-A2 positive, HER2 positive and disparate for SNP 1170) for spontaneous reactivity in the direction of the P-peptide, but also in the A-peptide direction; however, this has so far not been possible because of the lack of appropriate donor–recipient pairs. As our data show that the peptide is expressed in the context of HLA-A2 on the surface of HER2-positive cancer cells, we used EliSpot to study whether we could detect spontaneous T-cell responses in HER2-positive breast cancer patients. However, we were not able to detect such responses (data not shown). Natural immune responses are in most cases very weak, not comparable with responses directed against mHag after HCT; hence, these data are not conclusive with regard to potential relevance in HCT.

Hematopoietic cell transplantation represents a cellular treatment strategy with curative potential in several hematological indications. However, HCT is not unproblematic; first, its clinical efficacy varies immensely among indications, and for some the treatment is not curative. Moreover, the main adverse side effect—graft versus host (GVH) disease—may be life threatening, and even when manageable, is severely affecting the quality of life in many patients. Thus, characterization of mHags with a suited expression profile may aid the development of strategies that specifically target such mHags after HCT. Our data suggest that the reverse immunology strategy used for identification of the HER2_1170 mHag may set the stage for a more selective characterization of mHags with a focus on hematopoietic expression, tumor expression and function of the protein, as well as frequency of the restriction molecule and the SNP.

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Acknowledgements

This study was supported by grants from The Danielsen Foundation, The Novo Nordisk Foundation, Danish Medical Research Council, The Danish Cancer Society, The John and Birthe Meyer Foundation, and the Toyota Foundation.

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Authors and Affiliations

  1. Department of Hematology, Center for Cancer Immune Therapy (CCIT), Herlev University Hospital, Herlev, Denmark

    L Wenandy, T Kollgaard, R S Andersen, T Seremet, I M Svane, M H Andersen & P thor Straten

  2. Department of Hematology, Oncology, Charité, Berlin, Germany

    A Letsch & D Stather

  3. Department of Oncology, Herlev University Hospital, Herlev, Denmark

    I M Svane

  4. Department of Hematology, The Hematopoietic Cell Transplantation Laboratory, Rigshospitalet, Copenhagen, Denmark. E-mail: pethst01@heh.regionh.dk,

    L Vindeløv

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Wenandy, L., Kollgaard, T., Letsch, A. et al. The 1170 A–P single-nucleotide polymorphism (SNP) in the Her-2/neu protein (HER2) as a minor histocompatibility antigen (mHag). Leukemia 23, 1926–1929 (2009). https://doi.org/10.1038/leu.2009.112

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