? ? Recently, detection of autologous antibodies (Ab) in patients' sera against individual prostate cancer- associated antigens (PCAA) received renewed attention as a means to overcome the lack of specificity of the PSA test for early detection. However, to establish humoral responses against PCAA as a diagnostic tool, a large panel of clinically relevant PCAA is required. Purifying individual recombinant proteins of PCAA is not practical on large scales. To circumvent this obstacle, we used computer-assisted algorithms to predict B cell epitopes from prototypic PCAA, such as NY-ESO-1 and XAGE-1b. B cell epitopes from these PCAA can be rapidly identified and used for detection of antibody responses with similar frequencies and sensitivities as the full-length recombinant proteins. We hypothesize that B cell epitopes from clinically relevant PCAA can be compiled as an epitope array that will complement serum PSA tests for the early detection of prostate cancer and its recurrence. To test this hypothesis and to establish the epitope array technology for prostate cancer, we propose the following specific aims: 1). To identify linear B cell epitopes from a panel of clinically relevant PCAA, which are predicted to cover 95% of known prostate cancer patients with more than 85% specificities. 2). To assess the sensitivity and specificity for the retrospective detection of prostate cancer by epitope arrays. The diagnostic potential of epitope arrays will be compared with PSA tests in 46 prostate cancer patients with low to intermediate PSA levels. We will also test whether epitope arrays add additional power to PSA tests for detecting prostate cancer. This investigation will provide proof of principle that epitope arrays against clinically relevant PCAA are feasible approaches for detection of prostate cancer. This novel technology may complement PSA test for early detection of prostate cancer and its recurrence in the future. ? ? ?
| Xie, Chong; Kim, Hyun J; Haw, Jonathan G et al. (2011) A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases. J Transl Med 9:43 |
| Meng, Zhaoting; Wang, Yadong; Zhang, Guanzhong et al. (2011) Identification of an HLA-DPB1*0501 restricted Melan-A/MART-1 epitope recognized by CD4+ T lymphocytes: prevalence for immunotherapy in Asian populations. J Immunother 34:525-34 |
