Restifo N P, Rosenberg S A
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA.
Curr Opin Oncol. 1999 Jan;11(1):50-7. doi: 10.1097/00001622-199901000-00012.
To develop new vaccines for the treatment of patients with cancer, target antigens presented on tumor cell surfaces have been cloned. Many of these antigens are non-mutated differentiation antigens and are expressed by virtually all melanomas, making them attractive components for a widely efficacious melanoma vaccine. These antigens are also expressed by melanocytes, however, and are likely to be subject to immune tolerance. A central challenge for tumor immunologists has thus been the breaking of tolerance to cancer antigens. We review recent clinical trials using experimental cancer vaccines, including recent evidence that therapeutic vaccines can induce objective responses in patients with metastatic malignant melanoma. We focus on the foundations of these approaches in new experimental animal models designed to test novel vaccines and report on what these new models predict for the future development of therapeutic vaccines for cancer.
为研发用于治疗癌症患者的新型疫苗，肿瘤细胞表面呈现的靶抗原已被克隆。这些抗原中有许多是非突变的分化抗原，几乎所有黑色素瘤均表达这些抗原，这使其成为广泛有效的黑色素瘤疫苗的有吸引力的组成部分。然而，这些抗原也由黑素细胞表达，并且可能会受到免疫耐受。因此，肿瘤免疫学家面临的一个核心挑战是打破对癌症抗原的耐受性。我们回顾了使用实验性癌症疫苗的近期临床试验，包括近期关于治疗性疫苗可在转移性恶性黑色素瘤患者中诱导客观反应的证据。我们关注这些方法在旨在测试新型疫苗的新实验动物模型中的基础，并报告这些新模型对癌症治疗性疫苗未来发展的预测。
