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

Oncogene volume 23, pages 8859–8867 (2004)Cite this article

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.

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Acknowledgements

We thank Behrang Amini, Kim-Anh Do, Johanna Lahdenranta, Gordon B Mills, Angela D Thornton, and Sijin Wen for technical assistance, scientific advice, and reagents. This work was supported by the Specialized Program of Research Excellence (SPORE) in Ovarian Cancer of the National Cancer Institute (CA836393 to R Pasqualini) and awards from AngelWorks, the Gilson-Longenbaugh Foundation, and the V Foundation (to W Arap and R Pasqualini). CI Vidal is a recipient of a Bettyann Asche-Murray Fellowship from the Blanton-Davis Ovarian Cancer Research Program.

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Authors and Affiliations

  1. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Claudia I Vidal, Paul J Mintz, Wadih Arap & Renata Pasqualini

  2. Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Karen Lu & David M Gershenson

  3. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Lee M Ellis

  4. Department of Oncology, Laboratory of Biology and Therapy of Metastasis, Mario Negri Institute for Pharmacological Research, Bergamo, 24125, Italy

    Luigi Manenti & Raffaella Giavazzi

  5. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Russell Broaddus & Jinsong Liu

  6. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Wadih Arap & Renata Pasqualini

Authors
  1. Claudia I Vidal
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  2. Paul J Mintz
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  3. Karen Lu
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  4. Lee M Ellis
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  9. Jinsong Liu
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  10. Wadih Arap
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  11. Renata Pasqualini
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Correspondence to Wadih Arap or Renata Pasqualini.

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Vidal, C., Mintz, P., Lu, K. et al. An HSP90-mimic peptide revealed by fingerprinting the pool of antibodies from ovarian cancer patients. Oncogene 23, 8859–8867 (2004). https://doi.org/10.1038/sj.onc.1208082

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