Graddis Thomas J, McMahan Catherine J, Tamman Jennifer, Page Keith J, Trager James B
Department of Immunology, University of Washington, Seattle, WA, USA.
Int J Clin Exp Pathol. 2011 Mar;4(3):295-306. Epub 2011 Mar 22.
Prostate cancer is the most common cancer and the second leading cause of cancer deaths among males in most Western countries. Autologous cellular immunotherapy for the treatment of cancer seeks to induce tumor-specific immunity in the patient and is consequently dependent on a suitable target antigen and effective presentation of that antigen to the patient's immune system. Prostatic acid phosphatase (PAP) has been tested as a target antigen due to its high and apparently specific expression in the prostate. We used a variety of approaches to analyze PAP expression, including immunohistochemistry, in situ hybridization, and quantitative polymerase chain reaction. We complemented these laboratory-based techniques with an in silico analysis of reported PAP expression in human cDNA libraries. Our studies confirmed that, while PAP expression is not restricted to prostate tissues, its expression in other human tissues is approximately 1-2 orders of magnitude less than that observed in the prostate. The relative specificity of PAP expression in the prostate supports its use as a target of autologous cellular immunotherapy. The approach described here, involving the use of multiple correlates of tissue-specific expression, is warranted as a prerequisite in selecting any suitable target for immunotherapy.
前列腺癌是最常见的癌症，在大多数西方国家，它是男性癌症死亡的第二大主要原因。用于治疗癌症的自体细胞免疫疗法旨在诱导患者产生肿瘤特异性免疫，因此依赖于合适的靶抗原以及该抗原向患者免疫系统的有效呈递。前列腺酸性磷酸酶（PAP）因其在前列腺中高表达且明显具有特异性，已被作为靶抗原进行检测。我们使用了多种方法来分析PAP的表达，包括免疫组织化学、原位杂交和定量聚合酶链反应。我们通过对人类cDNA文库中报道的PAP表达进行计算机分析，对这些基于实验室的技术进行了补充。我们的研究证实，虽然PAP的表达并不局限于前列腺组织，但其在其他人体组织中的表达比在前列腺中观察到的表达低约1 - 2个数量级。PAP在前列腺中表达的相对特异性支持将其用作自体细胞免疫疗法的靶点。这里描述的方法，即使用组织特异性表达的多种相关指标，作为选择任何合适的免疫治疗靶点的先决条件是必要的。
