Summary
Development of humoral and cellular immunity against self-cellular proteins in cancer patients is a phenomenal observation. The ability of immune system to sense the presence of the disease and to fight of the disease by generating autoantibodies against tumor antigens makes it a natural biosensor. Several screening technologies have been employed for the identification of tumor-specific antibodies in cancer patients. We have developed a multidimensional approach for the identification of diagnostic antigens that utilizes a combination of high-throughput antigen cloning and protein microarray-based serological detection of complex panels of antigens by exploiting the serum autoantibody repertoire directed toward tumor-associated antigens in cancer patients. Furthermore, validation of these antigens by different bioinformatics and biological approaches will reveal the diagnostic/prognostic utility of these antigens for personalized immunotherapy.
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References
Anderson, K. S. and LaBaer, J. (2005) The sentinel within: exploiting the immune system for cancer biomarkers. J. Proteome. Res. 4, 1123–1133
Sahin, U., Tureci, O., Schmitt, H., Cochlovius, B., Johannes, T., Schmits, R., Stenner, F., Luo, G., Schobert, I., and Pfreundschuh, M. (1995) Human neoplasms elicit multiple specific immune responses in the autologous host. Proc. Natl Acad. Sci. U S A 92, 11810–11813
Disis, M. L., Calenoff, E., McLaughlin, G., Murphy, A. E., Chen, W., Groner, B., Jeschke, M., Lydon, N., McGlynn, E., Livingston, R. B., and Martin, A. C. (1994) Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res. 54, 16–20
Disis, M. L., Pupa, S. M., Gralow, J. R., Dittadi, R., Menard, S., and Cheever, M. A. (1997) High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J. Clin. Oncol. 15, 3363–3367
Gadducci, A., Ferdeghini, M., Buttitta, F., Cosio, S., Fanucchi, A., Annicchiarico, C., Gagetti, O., Bevilacqua, G., and Genazzani, A. R. (1999) Assessment of the prognostic relevance of serum anti-p53 antibodies in epithelial ovarian cancer. Gynecol. Oncol. 72, 76–81
Lechpammer, M., Lukac, J., Lechpammer, S., Kovacevic, D., Loda, M., and Kusic, Z. (2004) Humoral immune response to p53 correlates with clinical course in colorectal cancer patients during adjuvant chemotherapy. Int. J. Colorectal Dis. 19, 114–120
Conroy, S. E. and Latchman, D. S. (1996) Do heat shock proteins have a role in breast cancer? Br. J. Cancer 74, 717–721
Conroy, S. E., Sasieni, P. D., Fentiman, I., and Latchman, D. S. (1998) Autoantibodies to the 90kDa heat shock protein and poor survival in breast cancer patients. Eur. J. Cancer 34, 942–943
Sioud, M. and Hansen, M. H. (2001) Profiling the immune response in patients with breast cancer by phage-displayed cDNA libraries. Eur. J. Immunol. 31, 716–725
Nam, M. J., Madoz-Gurpide, J., Wang, H., Lescure, P., Schmalbach, C. E., Zhao, R., Misek, D. E., Kuick, R., Brenner, D. E., and Hanash, S. M. (2003) Molecular profiling of the immune response in colon cancer using protein microarrays: occurrence of autoantibodies to ubiquitin C-terminal hydrolase L3. Proteomics 3, 2108–2115
Brass, N., Racz, A., Bauer, C., Heckel, D., Sybrecht, G., and Meese, E. (1999) Role of amplified genes in the production of autoantibodies. Blood 93, 2158–2166
Naora, H., Yang, Y. Q., Montz, F. J., Seidman, J. D., Kurman, R. J., and Roden, R. B. (2001) A serologically identified tumor antigen encoded by a homeobox gene promotes growth of ovarian epithelial cells. Proc. Natl Acad. Sci. U S A 98, 4060–4065
Scanlan, M. J., Gout, I., Gordon, C. M., Williamson, B., Stockert, E., Gure, A. O., Jager, D., Chen, Y. T., Mackay, A., O’Hare, M. J., and Old, L. J. (2001) Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. Cancer Immun. 1, 4
Chen, Y. T., Scanlan, M. J., Sahin, U., Tureci, O., Gure, A. O., Tsang, S., Williamson, B., Stockert, E., Pfreundschuh, M., and Old, L. J. (1997) A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc. Natl Acad. Sci. U S A 94, 1914–1918
Jager, D., Stockert, E., Gure, A. O., Scanlan, M. J., Karbach, J., Jager, E., Knuth, A., Old, L. J., and Chen, Y. T. (2001) Identification of a tissue-specific putative transcription factor in breast tissue by serological screening of a breast cancer library. Cancer Res. 61, 2055–2061
Jongeneel, V. (2001) Towards a cancer immunome database. Cancer Immun. 1, 3
Scanlan, M. J., Gure, A. O., Jungbluth, A. A., Old, L. J., and Chen, Y. T. (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol. Rev. 188, 22–32
De, S. C., De, B. O., Faraoni, I., Lurquin, C., Brasseur, F., and Boon, T. (1996) The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc. Natl Acad. Sci. U S A 93, 7149–7153
Stockert, E., Jager, E., Chen, Y. T., Scanlan, M. J., Gout, I., Karbach, J., Arand, M., Knuth, A., and Old, L. J. (1998) A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. J. Exp. Med. 187, 1349–1354
Brass, N., Heckel, D., Sahin, U., Pfreundschuh, M., Sybrecht, G. W., and Meese, E. (1997) Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma. Hum. Mol. Genet. 6, 33–39
Stone, B., Schummer, M., Paley, P. J., Thompson, L., Stewart, J., Ford, M., Crawford, M., Urban, N., O’Briant, K., and Nelson, B. H. (2003) Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q. Int. J. Cancer 104, 73–84
Jager, D., Jager, E., and Knuth, A. (2001) Immune responses to tumour antigens: implications for antigen specific immunotherapy of cancer. J. Clin. Pathol. 54, 669–674
Chen, Y. T., Gure, A. O., Tsang, S., Stockert, E., Jager, E., Knuth, A., and Old, L. J. (1998) Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc. Natl Acad. Sci. U S A 95, 6919–6923
Chatterjee, M., Mohapatra, S., Ionan, A., Bawa, G., Ali-Fehmi, R., Wang, X., Nowak, J., Ye, B., Nahhas, F. A., Lu, K., Witkin, S. S., Fishman, D., Munkarah, A., Morris, R., Levin, N. K., Shirley, N. N., Tromp, G., Abrams, J., Draghici, S., and Tainsky, M. A. (2006) Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays. Cancer Res. 66, 1181–1190
Draghici, S., Chatterjee, M., and Tainsky, M. A. (2005) Epitomics: serum screening for the early detection of cancer on microarrays using complex panels of tumor antigens. Expert Rev. Mol. Diagn. 5, 735–743
Carmen, S. and Jermutus, L. (2002) Concepts in antibody phage display. Brief Funct. Genomic. Proteomic. 1, 189–203
Smith, G. P. and Petrenko, V. A. (1997) Phage display. Chem. Rev. 97, 391–410
Pepe, M. S., Longton, G., Anderson, G. L., and Schummer, M. (2003) Selecting differentially expressed genes from microarray experiments. Biometrics 59, 133–142
Angelopoulou, K., Yu, H., Bharaj, B., Giai, M., and Diamandis, E. P. (2000) p53 gene mutation, tumor p53 protein overexpression, and serum p53 autoantibody generation in patients with breast cancer. Clin. Biochem. 33, 53–62
Wang, X., Yu, J., Sreekumar, A., Varambally, S., Shen, R., Giacherio, D., Mehra, R., Montie, J. E., Pienta, K. J., Sanda, M. G., Kantoff, P. W., Rubin, M. A., Wei, J. T., Ghosh, D., and Chinnaiyan, A. M. (2005) Autoantibody signatures in prostate cancer. N. Engl. J. Med. 353, 1224–1235
Zhong, L., Hidalgo, G. E., Stromberg, A. J., Khattar, N. H., Jett, J. R., and Hirschowitz, E. A. (2005) Using protein microarray as a diagnostic assay for non-small cell lung cancer. Am. J. Respir. Crit Care Med. 172, 1308–1314
Acknowledgments
This work was supported by The Barbara and Fred Erb Endowed Chair in Cancer Genetics, The Gail Purtan Ovarian Cancer Research Fund, The Sinai Guild, and grants from The Michigan Life Science Corridor Fund 085P300470, NIH grant CA100740, NIH grant U01 CA117478-01, and The Susan G. Komen Breast Cancer Foundation grant BCTR0504211 (M.A.Tainsky).
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Chatterjee, M., Wojciechowski, J., Tainsky, M.A. (2009). Discovery of Antibody Biomarkers Using Protein Microarrays of Tumor Antigens Cloned in High Throughput. In: Tainsky, M. (eds) Tumor Biomarker Discovery. Methods in Molecular Biology, vol 520. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-811-9_3
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DOI: https://doi.org/10.1007/978-1-60327-811-9_3
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