Fingerprinting the circulating repertoire of antibodies from cancer patients

Paul J. Mintz, Jeri Kim, Kim Anh Do, Xuemei Wang, Ralph G. Zinner, Massimo Cristofanilli, Marco A. Arap, Waun Ki Hong, Patricia Troncoso, Christopher J. Logothetis, Renata Pasqualini, Wadih Arap*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

277 Scopus citations

Abstract

Recognition of molecular diversity in disease is required for the development of targeted therapies. We have developed a screening method based on phage display to select peptides recognized by the repertoire of circulating tumor-associated antibodies. Here we isolated peptides recognized by antibodies purified from the serum of prostate cancer patients. We identified a consensus motif, NXS/TDKS/T, that bound selectively to circulating antibodies from cancer patients over control antibodies from blood donors. We validated this motif by showing that positive serum reactivity to the peptide was specifically linked to disease progression and to shorter survival in a large patient population. Moreover, we identified the corresponding protein eliciting the immune response. Finally, we showed a strong and specific positive correlation between serum reactivity to the tumor antigen, development of metastatic androgen-independent disease, and shorter overall survival. Exploiting the differential humoral response to cancer through such an approach may identify molecular markers and targets for diagnostic and therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)57-63
Number of pages7
JournalNature biotechnology
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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