Department of General Surgery, Rush University Medical Center, Chicago, IL, USA.
Immunotherapy. 2012 Jan;4(1):27-42. doi: 10.2217/imt.11.160.
Renal cell carcinoma (RCC) is the most common primary malignancy affecting the kidney. In the past decade, several well-designed clinical trials have shifted the treatment paradigm for RCC to favor targeted therapies as first-line agents. Recognition of the immunogenic nature of RCC has also resulted in the development of immunotherapy approaches with high-dose IL-2 treatment being the best established and associated with durable disease control. The lack of defined antigens in RCC has hindered more specific vaccine development. TroVax(®) is a novel vaccine based on a modified vaccinia virus Ankara vector engineered to express the 5T4 tumor-associated antigen, found on over 95% of clear cell and papillary RCC tumors. The safety and efficacy of TroVax has been evaluated in several Phase I/II clinical trials and in a multicenter Phase III trial. This article will discuss the clinical background of RCC, the rationale for TroVax development, results of several TroVax clinical trials and future directions for optimizing TroVax therapy in patients with RCC and other cancers.
肾细胞癌 (RCC) 是最常见的原发性肾脏恶性肿瘤。在过去的十年中，几项精心设计的临床试验已经将 RCC 的治疗模式转变为以靶向治疗为一线药物。对 RCC 的免疫原性的认识也导致了免疫治疗方法的发展，其中高剂量 IL-2 治疗是最成熟的方法，与持久的疾病控制相关。RCC 中缺乏明确的抗原阻碍了更具特异性的疫苗开发。TroVax(®) 是一种新型疫苗，基于改良安卡拉痘苗病毒载体，工程设计表达 5T4 肿瘤相关抗原，该抗原存在于超过 95%的透明细胞和乳头状 RCC 肿瘤上。TroVax 的安全性和疗效已在几项 I/II 期临床试验和一项多中心 III 期试验中进行了评估。本文将讨论 RCC 的临床背景、TroVax 开发的原理、几项 TroVax 临床试验的结果以及优化 TroVax 治疗 RCC 和其他癌症患者的未来方向。
