State Key Laboratory of Biotherapy, West China Hospital and School of Life Science, Sichuan University Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China.
Cancer Sci. 2010 Nov;101(11):2325-32. doi: 10.1111/j.1349-7006.2010.01695.x.
Murine studies have shown that immunological targeting of fibroblast activation protein (FAP) can elicit protective immunity in the absence of significant pathology. Fibroblast activation protein is a product overexpressed by tumor-associated fibroblasts (TAF) and is the predominant component of the stoma in most types of cancer. Tumor-associated fibroblasts differ from normal adult tissue fibroblasts, and instead resemble transient fetal and wound healing-associated fibroblasts. Tumor-associated fibroblasts are critical regulators of tumorigenesis, but differ from tumor cells by being more genetically stable. Therefore, in comparison to tumor cells, TAF may represent more viable therapeutic targets for cancer immunotherapy. To specifically target TAF, we constructed a DNA vaccine directed against FAP. This vaccine significantly suppressed primary tumor and pulmonary metastases primarily through CD8(+) T-cell-mediated killing in tumor-bearing mice. Most importantly, tumor-bearing mice vaccinated against FAP exhibited a 1.5-fold increase in lifespan and no significant pathology. These results suggest that FAP, a product preferentially expressed by TAF, could function as an effective tumor rejection antigen.
鼠类研究表明，在没有明显病理变化的情况下，针对成纤维细胞激活蛋白（FAP）的免疫靶向治疗可以引发保护性免疫。成纤维细胞激活蛋白是肿瘤相关成纤维细胞（TAF）过度表达的产物，是大多数类型癌症中嵴的主要成分。肿瘤相关成纤维细胞与正常成人组织成纤维细胞不同，更类似于短暂的胎儿和成纤维细胞愈合相关的成纤维细胞。肿瘤相关成纤维细胞是肿瘤发生的关键调节因子，但与肿瘤细胞相比，它们的遗传稳定性更高。因此，与肿瘤细胞相比，TAF 可能是癌症免疫治疗更可行的治疗靶点。为了专门针对 TAF，我们构建了一种针对 FAP 的 DNA 疫苗。该疫苗在荷瘤小鼠中主要通过 CD8+T 细胞介导的杀伤显著抑制了原发性肿瘤和肺转移。最重要的是，接种 FAP 疫苗的荷瘤小鼠的寿命延长了 1.5 倍，且没有明显的病理变化。这些结果表明，FAP 作为 TAF 优先表达的产物，可以作为有效的肿瘤排斥抗原。
