Department of Endocrinology and Medical Oncology, Genitourinary Cancer Section, University Federico II, Via Pansini 5, Naples, Italy.
Nat Rev Clin Oncol. 2011 May 24;8(9):551-61. doi: 10.1038/nrclinonc.2011.72.
Failure of immune surveillance has a prominent role in tumorigenesis. Cancerous cells can evade T-cell responses to tumor-associated antigens by multiple mechanisms. Active immunotherapy aims to stimulate the immune response against cancer cells. Unlike normal prostate tissue, prostate cancer is not ignored by the immune system, as shown by the presence of tumor infiltrating lymphocytes. This characteristic renders prostate cancer particularly suitable for immunotherapy. The existence of well-defined antigens, largely limited to prostate tissue, allows prostate cancer cells to be targeted without the risk of systemic autoimmune reactions, as autoimmunity specifically directed at the prostate is the goal of prostate cancer immunotherapy. Active immunotherapy directed towards prostate cancer can be conducted using multiple strategies, involving dendritic cells, whole-cell vaccines, viral vectors, DNA-based and peptide-based agents, as well as immunostimulatory agents. The only FDA-approved immunotherapy for prostate cancer is the dendritic-cell-based agent Sipuleucel-T, which yielded an advantage in overall survival, but not in progression-free survival in a phase III trial. We present the clinical developments in the field of immunotherapy and critically analyze methodological issues related to the evaluation of tumor responses to immunotherapy, trial design, and surrogate end points.
免疫监视的失败在肿瘤发生中起着重要作用。癌细胞可以通过多种机制逃避 T 细胞对肿瘤相关抗原的反应。主动免疫疗法旨在刺激针对癌细胞的免疫反应。与正常前列腺组织不同，前列腺癌不会被免疫系统忽视，因为肿瘤浸润淋巴细胞的存在表明了这一点。这一特征使得前列腺癌特别适合免疫治疗。由于明确的抗原存在，主要局限于前列腺组织，因此可以靶向前列腺癌细胞，而不会有全身自身免疫反应的风险，因为针对前列腺的自身免疫是前列腺癌免疫治疗的目标。针对前列腺癌的主动免疫疗法可以通过多种策略进行，包括树突状细胞、全细胞疫苗、病毒载体、基于 DNA 和基于肽的制剂以及免疫刺激剂。唯一获得 FDA 批准用于前列腺癌的免疫疗法是基于树突状细胞的 Sipuleucel-T，该疗法在 III 期临床试验中在总生存期方面具有优势，但在无进展生存期方面没有优势。我们介绍了免疫治疗领域的临床进展，并批判性地分析了与评估免疫治疗对肿瘤反应、试验设计和替代终点相关的方法学问题。
