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Lack of effective T-lymphocyte response to the PAX3/FKHR translocation area in alveolar rhabdomyosarcoma

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Abstract

Purpose: Alveolar rhabdomyosarcoma (ARMS) frequently contains the fusion transcription factor PAX3/FKHR. Therefore, clinical studies have been initiated to utilize the PAX3/FKHR translocation point area as a peptide vaccine against ARMS. Our study was directed at identifying antigenic T-lymphocyte epitopes at the PAX3/FKHR translocation point area. Experimental design: The peptide sequence surrounding the PAX3/FKHR translocation point was evaluated by MHC binding algorithms for potential T-lymphocyte antigenic epitopes (class I molecules HLA-A1, -A2 and -A3; class II molecules HLA-DR1, -DR4 and -DR7). Using in vitro techniques, dendritic cells loaded with PAX3/FKHR peptides were used to stimulate naïve T-lymphocytes. T-lymphocyte activity was then evaluated by 51Cr release and 3H-thymidine uptake assays. Results: Only one HLA-A3-restricted epitope was predicted by the algorithms. The peptide was prepared and tested for its ability to stimulate naïve cytotoxic T-lymphocytes (CTLs). Unfortunately, the peptide was unsuccessful at stimulating naïve CTL. However, induction of naïve helper T-lymphocytes (HTL) to recognize and respond to the PAX3/FKHR translocation peptide was successful. Yet, this HTL peptide activity did not translate into recognition of PAX3/FKHR-containing ARMS tumor cells. Conclusions: It appears that the fusion area of PAX3/FKHR may not be a good source of antigenic anti-tumor peptide epitopes. These results raise serious concerns about the success and applicability of future peptide-based vaccine immunotherapy directed at the PAX3/FKHR translocation point.

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Authors and Affiliations

  1. Department of Surgery, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA

    David A. Rodeberg & Rebecca A. Nuss

  2. Departments of Immunology, Mayo Clinic and Foundation, Rochester, MN, 55905, USA

    Carrie J. Heppelmann & Esteban Celis

Authors
  1. David A. Rodeberg
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  2. Rebecca A. Nuss
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  3. Carrie J. Heppelmann
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  4. Esteban Celis
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Correspondence to David A. Rodeberg.

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Rodeberg, D.A., Nuss, R.A., Heppelmann, C.J. et al. Lack of effective T-lymphocyte response to the PAX3/FKHR translocation area in alveolar rhabdomyosarcoma. Cancer Immunol Immunother 54, 526–534 (2005). https://doi.org/10.1007/s00262-004-0625-6

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  • DOI: https://doi.org/10.1007/s00262-004-0625-6

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