Kiessling Andrea, Füssel Susanne, Schmitz Marc, Stevanovic Stefan, Meye Axel, Weigle Bernd, Klenk Ulrich, Wirth Manfred P, Rieber Ernst P
Institute of Immunology, Medical Faculty, Technical University of Dresden, Dresden, Germany.
Prostate. 2003 Sep 1;56(4):270-9. doi: 10.1002/pros.10265.
New concepts for the immunotherapy of prostate carcinoma (PCa) largely depend on the identification of suitable target antigens that are present in a high percentage of prostate tumors. Their expression in normal tissues should be restricted to the prostate and they should be immunogenic in vivo. The number of antigens displaying these properties is still limited. Here, we identify for the first time an immunogenic peptide derived from the prostate-specific protein transient receptor potential-p8 (trp-p8) that is recognized by cytotoxic T lymphocytes (CTLs) from PCa patients.
To determine the abundance of trp-p8 in prostate tumors, the expression level of trp-p8 mRNA was quantitatively analyzed in a panel of prostate cancer tissues. Trp-p8-derived human leukocyte antigen (HLA)-A*0201-restricted peptides were selected and tested for the in vitro activation of CTLs when loaded on autologous dendritic cells (DCs).
Trp-p8 mRNA was found to be expressed in all prostate tumors and in the corresponding normal prostate tissue. Of five selected trp-p8-derived peptides, only peptide GLMKYIGEV was shown to activate specific CTLs, which effectively lysed PCa cells confirming the endogenous generation and presentation of this peptide by tumor cells.
Our results suggest this antigen as a suitable target for the T-cell-based immunotherapy of PCa.
前列腺癌（PCa）免疫治疗的新概念很大程度上依赖于鉴定在高比例前列腺肿瘤中存在的合适靶抗原。它们在正常组织中的表达应局限于前列腺，并且在体内应具有免疫原性。显示这些特性的抗原数量仍然有限。在此，我们首次鉴定出一种源自前列腺特异性蛋白瞬时受体电位-p8（trp-p8）的免疫原性肽，该肽可被PCa患者的细胞毒性T淋巴细胞（CTL）识别。
为了确定trp-p8在前列腺肿瘤中的丰度，在一组前列腺癌组织中对trp-p8 mRNA的表达水平进行了定量分析。选择了trp-p8衍生的人类白细胞抗原（HLA）-A*0201限制性肽，并在加载到自体树突状细胞（DC）上时测试其对CTL的体外激活作用。
发现trp-p8 mRNA在所有前列腺肿瘤和相应的正常前列腺组织中均有表达。在五个选定的trp-p8衍生肽中，只有肽GLMKYIGEV显示出能激活特异性CTL，其可有效裂解PCa细胞，证实了该肽由肿瘤细胞内源性产生和呈递。
我们的结果表明该抗原是PCa基于T细胞免疫治疗的合适靶点。
