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.
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Acknowledgements
We thank Drs. Ricardo R. Brentani, Isaiah J. Fidler, and Donald M. McDonald for comments on the manuscript, and Mary and Howard Lester for support. Supported by grants from NIH (CA90270 and CA8297601 to R.P., CA90270 and CA9081001 to W.A.) and awards from the Gilson-Longenbaugh Foundation, AngelWorks Foundation, and CaP CURE (to R.P. and W.A.). P.J.M. is the recipient of a fellowship from the Susan G. Komen Breast Cancer Foundation.
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The University of Texas and its researchers W.A. and R.P. have equity in NTTX Biotechnology, which is subject to certain restrictions under university policy. The University of Texas manages the terms of these arrangements in accordance with its conflict-of-interest policies.
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Mintz, P., Kim, J., Do, KA. et al. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat Biotechnol 21, 57–63 (2003). https://doi.org/10.1038/nbt774
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DOI: https://doi.org/10.1038/nbt774
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