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Fingerprinting the circulating repertoire of antibodies from cancer patients

Nature Biotechnology volume 21, pages 57–63 (2003)Cite this article

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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Figure 1: Strategy and screening of index patients.
Figure 2: Reactivity between the serum from prostate cancer patients or control men and the selected peptide is stage-specific.
Figure 3: Immunohistological analyses of tumors from individuals with prostate cancer.
Figure 4: Identification of the corresponding antigen.
Figure 5: Cross-inhibition of binding activity of the patient-derived serum by GRP78 or CNVSDKSC.
Figure 6: Reactivity against GRP78 is a candidate marker of prostate cancer.
Figure 7: Expression pattern of the protein GRP78 and specific immunostaining inhibition.

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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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Authors and Affiliations

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

    Paul J. Mintz, Jeri Kim, Marco A. Arap, Christopher J. Logothetis, Renata Pasqualini & Wadih Arap

  2. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX

    Kim-Anh Do & Xuemei Wang

  3. Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX

    Ralph G. Zinner & Waun Ki Hong

  4. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX

    Massimo Cristofanilli

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

    Patricia Troncoso

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

    Renata Pasqualini & Wadih Arap

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Correspondence to Wadih Arap.

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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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