Cathepsin D antigenic epitopes identified by the humoral responses of ovarian cancer patients

Sreenavasa R. Chinni, Çiçek Gerçel-Taylor, Gregory E. Conner, Douglas D. Taylor

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Previous studies implicated cathepsin D as one commonly recognized target of tumor-reactive immunoglobulins from ovarian cancer patients. These immunoglobulins are shown to be immunoreactive with both 52-kDa procathepsin D and the 32-kDa mature cathepsin D derived from the UL-1 ovarian cancer cell line. Whether the carbohydrate domains or the core protein were associated with its immunogenicity was analyzed with cathepsin D isolated from tunicamycin-treated UL-1 cells. No significant difference was detected in the immunoreactivity of patient serum with the glycosylated and deglycosylated forms of the cathepsin D, suggesting that patient humoral responses are directed primarily against the core protein. To define the antigenic epitopes of cathepsin D, tryptic fragments were prepared from UL-1-derived procathepsin D. The epitopes of the core protein recognized by sera from more than one patient were identified using a peptide-specific enzyme-linked immunosorbent assay and micro-sequencing of positive immunoreactive peptides. This protocol identified four epitopes: two peptides within the pro-peptide, a third at the carboxy terminus and the fourth at the glycosylation site of the mature enzyme. This approach to the identification of specific antigenic epitopes may be useful in defining effective targets for directed active immunotherapy againts cancer.

Original languageEnglish (US)
Pages (from-to)48-54
Number of pages7
JournalCancer Immunology Immunotherapy
Volume46
Issue number1
DOIs
StatePublished - 1998

Keywords

  • Autoantigens
  • Cathepsin D
  • Epitopes

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

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