Cancer Immunology, Immunotherapy

, Volume 62, Issue 12, pp 1831–1840

Development of a peptide-based vaccine targeting TMPRSS2:ERG fusion-positive prostate cancer

  • Haydn Thomas Kissick
  • Martin George Sanda
  • Laura Kathleen Dunn
  • Mohamed Simo Arredouani
Original Article

Abstract

Identification of novel vaccine targets is critical for the design and advancement of prostate cancer (PCa) immunotherapy. Ideal targets are proteins that are abundant in prostate tumors while absent in extra-prostatic tissues. The fusion of the androgen-regulated TMPRSS2 gene with the ETS transcription factor ERG occurs in approximately 50 % of prostate cancer cases and results in aberrant ERG expression. Because expression of ERG is very low in peripheral tissue, we evaluated the suitability of this protein as an antigen target in PCa vaccines. ERG-derived HLA-A*0201-restricted immunogenic epitopes were identified through a 3-step strategy that included in silico, in vitro, and in vivo validation. Algorithms were used to predict potential HLA-A*0201-binding epitopes. High-scoring epitopes were tested for binding to HLA-A*0201 using the T2-based stabilization assay in vitro. Five peptides were found to bind HLA-A*0201 and were subsequently tested for immunogenicity in humanized, HLA-A*0201 transgenic mice. The in vivo screening identified three immunogenic peptides. One of these peptides, ERG295, overcame peripheral tolerance in HLA-A*0201 mice that expressed prostate-restricted ERG. Also, this peptide induced an antigen-specific response against ERG-expressing human prostate tumor cells. Finally, tetramer assay showed detectable and responsive ERG295-specific cytotoxic lymphocytes in peripheral blood of HLA-A*0201+ prostate cancer patients. Detection of ERG-specific CTLs in both mice and the blood of prostate cancer patients indicates that ERG-specific tolerance can be overcome. Additionally, these data suggest that ERG is a suitable target antigen for PCa immunotherapy.

Keywords

Prostate cancer Vaccine ERG Epitope 

Supplementary material

262_2013_1482_MOESM1_ESM.pdf (299 kb)
Supplementary material 1 (PDF 299 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Haydn Thomas Kissick
    • 1
  • Martin George Sanda
    • 1
  • Laura Kathleen Dunn
    • 1
  • Mohamed Simo Arredouani
    • 1
  1. 1.Urology Division, Department of Surgery, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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