Albers Andreas E, Kaufmann Andreas M
Department of Otolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Public Health Genomics. 2009;12(5-6):331-42. doi: 10.1159/000214923. Epub 2009 Aug 11.
Despite impressive progress in prevention and therapy of premalignant and malignant dysplasia the worldwide burden of cancer is relatively unchanged. Supplementation of the therapeutic arsenal by immunotherapeutic methods would have the potential to make a significant impact. Dysplastic lesions and cancer of the cervix show strong association with human papillomaviruses (HPV), as do tumours of other mucosal epithelia like squamous cell carcinoma of the head and neck. Such tumours are distinct from most other malignancies in that they harbour foreign antigens derived from the virus. The expression of viral oncogenes is necessary to maintain the cancerous phenotype. Therefore, these antigens are unique to the tumour and very attractive targets for 'proof of concept' studies in the development of therapeutic vaccines showing the general applicability of tumour vaccination and prove the correlation of immune response and clinical response. To date numerous clinical trials have been performed with candidate vaccines predominantly for cervical cancer and its precursors. Although a naturally induced anti-HPV T cell response in patients can be shown, the success of therapeutic vaccines has so far been limited. This can probably be attributed to immunosuppression, immunoselection and immunoediting of the tumour cells and other, mostly unknown, factors of the individual contributing to the failure of autonomous clearance of the infection. Overriding this failure, reversing immunosuppression and application in early stages of the disease are the key tasks for future development of therapeutic vaccines. This review will summarize the basis and recent developments of therapeutic vaccines and discuss obstacles that hinder their success.
尽管在癌前病变和恶性发育异常的预防与治疗方面取得了令人瞩目的进展，但全球癌症负担相对未变。通过免疫治疗方法扩充治疗手段有可能产生重大影响。宫颈发育异常病变和癌症与人乳头瘤病毒（HPV）密切相关，头颈部鳞状细胞癌等其他黏膜上皮肿瘤也是如此。这类肿瘤与大多数其他恶性肿瘤不同，它们含有源自病毒的外来抗原。病毒癌基因的表达对于维持癌性表型是必要的。因此，这些抗原是肿瘤特有的，是治疗性疫苗“概念验证”研究极具吸引力的靶点，显示了肿瘤疫苗接种的普遍适用性，并证明了免疫反应与临床反应之间的相关性。迄今为止，已经针对主要用于宫颈癌及其前驱病变的候选疫苗开展了大量临床试验。虽然可以在患者中显示出自然诱导的抗HPV T细胞反应，但治疗性疫苗的成功迄今仍有限。这可能归因于肿瘤细胞的免疫抑制、免疫选择和免疫编辑以及个体中其他大多未知的因素导致感染自主清除失败。克服这一失败、逆转免疫抑制并在疾病早期应用是治疗性疫苗未来发展的关键任务。本综述将总结治疗性疫苗的基础和最新进展，并讨论阻碍其成功的障碍。
