Recognition of six-transmembrane epithelial antigen of the prostate-expressing tumor cells by peptide antigen-induced cytotoxic T lymphocytes

David A. Rodeberg, Rebecca A. Nuss, Sherine F. Elsawa, Esteban Celis

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The identification of novel markers and therapeutic targets in advanced cancer is critical for improving diagnosis and therapy. Six-transmembrane epithelial antigen of the prostate (STEAP) is expressed predominantly in human prostate tissue and in other common malignancies including prostate, bladder, colon, and ovarian carcinomas, and in Ewing's sarcoma, suggesting that it could function as an almost universal tumor antigen. We have used MHC peptide binding algorithms to predict potential STEAP sequences capable of stimulating in vitro naïve HLA-A2 - restricted CTLs. Four of six peptides predicted by these algorithms were able to induce antigen-specific CTLs that killed peptide-pulsed HLA-A2 target cells. Two of these peptides, STEAP-292 (MIAVFLPIV) and a modification of this peptide STEAP-292.2L (MLAVFLPIV), were the most efficient in the induction of primary CTL responses. More importantly, these CTLs were able to respond to tumor cells that express HLA-A2 and STEAP (colon, bladder, prostate, Ewing's sarcoma, and melanoma). Our results provide strong evidence that STEAP-292 is naturally processed by many tumor types and is presented in the context of HLA-A2 in sufficient amounts to allow recognition by CTLs. Also because STEAP-292.2L is a more immunogenic peptide able to induce CTL recognition of these STEAP-containing tumors and may have potential as an antitumor peptide vaccine.

Original languageEnglish (US)
Pages (from-to)4545-4552
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number12
DOIs
StatePublished - Jun 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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