An HSP90-mimic peptide revealed by fingerprinting the pool of antibodies from ovarian cancer patients

Claudia I. Vidal, Paul J. Mintz, Karen Lu, Lee M. Ellis, Luigi Manenti, Raffaella Giavazzi, David M. Gershenson, Russell Broaddus, Jinsong Liu, Wadih Arap, Renata Pasqualini

Research output: Contribution to journalArticle

Abstract

To gain insight into the mechanisms of molecular recognition and humoral immune response in ovarian cancer, we used fingerprinting, a phage display-based combinatorial selection to isolate peptide ligands to tumor-related antibodies present in ascites from patients with advanced disease. First, we have isolated a consensus motif (sequence CVPELGHEC) in 86% of the peptides screened; this enriched motif was selected from a total of 108-109 unique random sequences present in the library. Next, we identified the heat-shock protein 90 kDa (HSP90) as the native antigen mimicked by the motif. Finally, we evaluated the expression of HSP90 and the presence of antibodies against the HSP90-mimic peptide in a large panel of ovarian cancer patients and controls. In tissue microarrays, we show that the expression of HSP90 is ubiquitous. However, the corresponding humoral immune response against HSP90 is restricted to a subset of patients with stage IV disease. Together, these results show that screening humoral response can identify tumor antigens that may serve as molecular targets in ovarian cancer. Recognition of such relevant proteins in the immunobiology of malignant tumors may lead to the development of therapies.

Original languageEnglish
Pages (from-to)8859-8867
Number of pages9
JournalOncogene
Volume23
Issue number55
DOIs
Publication statusPublished - Nov 25 2004

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Keywords

  • Antibodies
  • Heat-shock proteins
  • HSP90
  • Ovarian cancer
  • Phage display

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Vidal, C. I., Mintz, P. J., Lu, K., Ellis, L. M., Manenti, L., Giavazzi, R., Gershenson, D. M., Broaddus, R., Liu, J., Arap, W., & Pasqualini, R. (2004). An HSP90-mimic peptide revealed by fingerprinting the pool of antibodies from ovarian cancer patients. Oncogene, 23(55), 8859-8867. https://doi.org/10.1038/sj.onc.1208082