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基于病毒载体的治疗性癌症疫苗。

Viral vector-based therapeutic cancer vaccines.

机构信息

Howard Hughes Medical Institute, Research Scholars' Program at the NIH, Bethesda, MD, USA.

出版信息

Cancer J. 2011 Sep-Oct;17(5):359-71. doi: 10.1097/PPO.0b013e3182325e63.

Abstract

Most viruses are naturally immunogenic and can be engineered to express tumor antigen transgenes. Moreover, many types of recombinant viruses have been shown to infect professional antigen-presenting cells, specifically dendritic cells, and express their transgenes. This enhanced presentation of tumor antigens to the immune system has led to an increase in the frequency and avidity of cytotoxic T lymphocytes that target tumor cells expressing the tumor antigen(s) encoded in the vaccine vector. Logistically, recombinant viruses can be produced, administered, and quality controlled more easily compared with other immunotherapy strategies. The intrinsic properties of each virus have distinct advantages and disadvantages, which can determine their applicability in a particular therapeutic setting. The disadvantage of some vectors is the development of host-induced neutralizing antibodies to the vector itself, thus limiting its continued use. The "off-the-shelf" nature of viral vaccine platforms renders them exceptionally suitable for multicenter randomized trials. This review described and discussed the strategies used and results using viral-based vaccines, with emphasis on phases II and III clinical trials. Future directions will involve the evaluation of viral-based vaccines in the adjuvant and neoadjuvant settings, in patients with low burden metastatic disease, and in combination with other forms of therapy including immunotherapy.

摘要

大多数病毒具有天然的免疫原性,可以被设计来表达肿瘤抗原转基因。此外,许多类型的重组病毒已被证明能够感染专业的抗原提呈细胞,特别是树突状细胞,并表达其转基因。这种对肿瘤抗原的递呈增强导致了靶向表达疫苗载体中编码的肿瘤抗原的肿瘤细胞的细胞毒性 T 淋巴细胞的频率和亲和力增加。从物流角度来看,与其他免疫疗法策略相比,重组病毒更容易生产、管理和质量控制。每种病毒的固有特性都有其独特的优缺点,这决定了它们在特定治疗环境中的适用性。一些载体的缺点是宿主产生针对载体本身的中和抗体,从而限制了其继续使用。病毒疫苗平台的“现货供应”性质使它们非常适合多中心随机临床试验。本文描述并讨论了使用病毒疫苗的策略和结果,重点是 II 期和 III 期临床试验。未来的方向将涉及评估辅助和新辅助环境、低负荷转移性疾病患者以及与其他形式的治疗(包括免疫疗法)联合使用病毒疫苗。

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