Wurz Gregory T, Kao Chiao-Jung, Wolf Michael, DeGregorio Michael W
a University of California , Davis; Department of Internal Medicine; Division of Hematology and Oncology ; Sacramento , CA USA.
Hum Vaccin Immunother. 2014;10(11):3383-93. doi: 10.4161/hv.29836.
The identification of tumor-associated antigens (TAA) has made possible the development of antigen-specific cancer immunotherapies such as tecemotide. One of those is mucin 1 (MUC1), a cell membrane glycoprotein expressed on some epithelial tissues such as breast and lung. In cancer, MUC1 becomes overexpressed and aberrantly glycosylated, exposing the immunogenic tandem repeat units in the extracellular domain of MUC1. Designed to target tumor associated MUC1, tecemotide is being evaluated in Phase III clinical trials for treatment of unresectable stage IIIA/IIIB non-small cell lung cancer (NSCLC) as maintenance therapy following chemoradiotherapy. Additional Phase II studies in other indications are ongoing. This review discusses the preclinical and clinical development of tecemotide, ongoing preclinical studies of tecemotide in human MUC1 transgenic mouse models of breast and lung cancer, and the potential application of these models for optimizing the timing of chemoradiotherapy and tecemotide immunotherapy to achieve the best treatment outcome for patients.
肿瘤相关抗原（TAA）的鉴定使得诸如替西莫肽等抗原特异性癌症免疫疗法的开发成为可能。其中之一是粘蛋白1（MUC1），一种在某些上皮组织（如乳腺和肺）上表达的细胞膜糖蛋白。在癌症中，MUC1会过度表达并发生异常糖基化，从而暴露MUC1细胞外结构域中的免疫原性串联重复单元。替西莫肽旨在靶向肿瘤相关的MUC1，目前正在进行III期临床试验，以评估其作为放化疗后的维持疗法用于治疗不可切除的IIIA/IIIB期非小细胞肺癌（NSCLC）。针对其他适应症的II期研究也在进行中。本综述讨论了替西莫肽的临床前和临床开发、替西莫肽在人MUC1转基因乳腺癌和肺癌小鼠模型中的临床前研究进展，以及这些模型在优化放化疗和替西莫肽免疫治疗时间以实现患者最佳治疗效果方面的潜在应用。
