Velders M P, Schreiber H, Kast W M
Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University, Chicago, Maywood, IL 60153, USA.
Semin Oncol. 1998 Dec;25(6):697-706.
Immunotherapy of cancer is still mainly an experimental treatment. Some monoclonal antibodies have been approved for adjuvant therapy of cancer in patients, but active immunization strategies have not yet matured to this stage. The fact that vaccination against viral diseases is effective has primed high expectations for successful vaccination against cancer as well. Indeed, in some animal models, therapeutic results could be obtained against short-term established tumors, which paved the way for clinical trials. However, the first results with active immunization in cancer patients were disappointing and this led to a careful examination of current protocols and the search for more effective approaches. Evaluation of the available data suggests that cancer patients may not be comparable in their immune response to cancer vaccines with healthy persons. Furthermore, the tumor seems to be able to develop several immune-escape mechanisms, which either inactivate the specific immune cells or prevent activation of potential effector mechanisms against the tumor. Here, we review the impediments that have been identified in murine models and clinical trials for immunotherapy of cancer. It will be important to study the hurdles to come to a better understanding of the immune evasion of tumors and to achieve efficient activation of the immune system in cancer patients against the tumor. This knowledge will open new possibilities for active immunization against cancer.
癌症免疫疗法目前仍主要处于实验性治疗阶段。一些单克隆抗体已被批准用于癌症患者的辅助治疗,但主动免疫策略尚未发展到这一阶段。鉴于针对病毒性疾病的疫苗接种有效,人们对成功的癌症疫苗接种也寄予了厚望。事实上,在一些动物模型中,针对短期形成的肿瘤能够取得治疗效果,这为临床试验铺平了道路。然而,癌症患者主动免疫的初步结果令人失望,这促使人们仔细审视当前的方案并寻找更有效的方法。对现有数据的评估表明,癌症患者对癌症疫苗的免疫反应可能与健康人不同。此外,肿瘤似乎能够发展出多种免疫逃逸机制,这些机制要么使特定免疫细胞失活,要么阻止针对肿瘤的潜在效应机制的激活。在此,我们综述了在小鼠模型和癌症免疫治疗临床试验中已发现的障碍。研究这些障碍对于更好地理解肿瘤的免疫逃逸以及实现癌症患者免疫系统针对肿瘤的有效激活至关重要。这些知识将为癌症主动免疫开辟新的可能性。