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

David A. Rodeberg, Rebecca A. Nuss, Carrie J. Heppelmann, Esteban Celis

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)526-534
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume54
Issue number6
DOIs
Publication statusPublished - Jun 1 2005
Externally publishedYes

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Keywords

  • Cancer vaccine
  • Cytotoxic T-lymphocyte
  • Dendritic cell
  • Helper T-lymphocyte
  • Peptide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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