Nature Biotechnology
21, 57 - 63 (2002)
Published online: 23 December 2002; | doi:10.1038/nbt774
Fingerprinting the circulating repertoire of antibodies from cancer patientsPaul J. Mintz1, Jeri Kim1, Kim-Anh Do2, Xuemei Wang2, Ralph G. Zinner3, Massimo Cristofanilli4, Marco A. Arap1, Waun Ki Hong3, Patricia Troncoso5, Christopher J. Logothetis1, Renata Pasqualini1, 6
& Wadih Arap1, 61
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. 2
Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. 3
Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. 4
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. 5
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. 6
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Correspondence should be addressed to Wadih Arap warap@notes.mdacc.tmc.eduRecognition 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.
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