Graham R A, Burchell J M, Taylor-Papadimitriou J
Epithelial Cell Biology, Imperial Cancer Research Fund, London, UK.
Cancer Immunol Immunother. 1996 Feb;42(2):71-80. doi: 10.1007/s002620050254.
The identification and cloning of several tumour antigens together with an improvement in the understanding of the mechanisms involved in antigen presentation and immune recognition has opened up the possibility of using active specific immunotherapy as a treatment for certain cancers. This review discusses the tumour-associated MUC1 gene product of the polymorphic epithelial mucin (PEM), as a potential target molecule for cancer treatment. PEM is both over-expressed and aberrantly glycosylated in many carcinomas resulting in an antigenically distinct molecule. Furthermore, immune responses specific for PEM have been detected in cancer patients. Both syngeneic and transgenic murine model systems have been developed in order to compare the efficacy and toxicity of various PEM-based immunogens in tumour rejection studies, and to further improve the understanding of antigen presentation and the mechanisms underlying tumour rejection. Such models also allow the examination of MUC1-based immunogens as a treatment for existing tumours. Clinical trials in progress using immunogens based on the MUC1 gene product are briefly discussed.
几种肿瘤抗原的鉴定与克隆,以及对抗抗原呈递和免疫识别所涉及机制理解的提升,开启了将主动特异性免疫疗法用作某些癌症治疗手段的可能性。本综述讨论了多形上皮粘蛋白(PEM)的肿瘤相关MUC1基因产物,将其作为癌症治疗的潜在靶分子。PEM在许多癌组织中均有过表达且糖基化异常,从而产生一种抗原性不同的分子。此外,在癌症患者中已检测到针对PEM的免疫反应。为了在肿瘤排斥研究中比较各种基于PEM的免疫原的疗效和毒性,并进一步增进对抗抗原呈递及肿瘤排斥潜在机制的理解,已经开发了同基因和转基因小鼠模型系统。此类模型还允许研究基于MUC1的免疫原作为现有肿瘤的一种治疗方法。本文简要讨论了正在进行的使用基于MUC1基因产物的免疫原的临床试验。