Rush University Cancer Center, Chicago, IL 60612, USA.
Semin Oncol. 2012 Jun;39(3):263-75. doi: 10.1053/j.seminoncol.2012.02.011.
The inherent immunogenicity of melanoma and renal cell carcinoma (RCC) has made these tumors a focus of considerable research in vaccine development. Recent data from murine studies of immunosurveillance have highlighted the importance of both innate and adaptive immune responses in shaping a tumor's inherent susceptibility to immune surveillance and immunotherapy. Melanoma has been a useful model for the identification of tumor-associated antigens and a number of putative renal cell antigens have been described more recently. These antigens have been targeted using a variety of vaccine strategies, including protein- and peptide-based vaccines, recombinant antigen-expressing vectors, and whole cell vaccine approaches. While evidence for clinical benefit has been disappointing to date, several current phase III clinical trials are in progress based on promising results from phase II studies. Accumulating data suggest that the tumor microenvironment and mechanisms of immunological escape by established tumors are significant barriers that must be overcome before vaccine therapy can be fully realized. This review will discuss the basis for vaccine development, describe some of the more promising vaccine strategies in development, and mention some of the tumor escape mechanisms that block effective anti-tumor immunity for melanoma and RCC.
黑色素瘤和肾细胞癌（RCC）的固有免疫原性使得这些肿瘤成为疫苗开发研究的重点。最近来自于免疫监视的鼠类研究数据强调了固有免疫和适应性免疫应答在塑造肿瘤对免疫监视和免疫治疗的固有敏感性方面的重要性。黑色素瘤一直是鉴定肿瘤相关抗原的有用模型，最近也描述了一些可能的肾细胞抗原。已经使用多种疫苗策略来靶向这些抗原，包括基于蛋白质和肽的疫苗、表达重组抗原的载体和全细胞疫苗方法。尽管迄今为止临床获益的证据令人失望，但基于 II 期研究的有希望的结果，目前正在进行几项 III 期临床试验。积累的数据表明，肿瘤微环境和已建立的肿瘤的免疫逃逸机制是重要的障碍，在疫苗治疗能够完全实现之前必须克服这些障碍。这篇综述将讨论疫苗开发的基础，描述一些正在开发的更有前途的疫苗策略，并提到一些阻止黑色素瘤和 RCC 有效抗肿瘤免疫的肿瘤逃逸机制。
