文章：

DNA疫苗：激活有效免疫对抗癌症的精密工具

DNA vaccines: precision tools for activating effective immunity against cancer

原文发布日期：2008-02-01

DOI: 10.1038/nrc2326

类型: Review Article

开放获取: 否

要点：

1. Preventative vaccination against infectious organisms has had a dramatic effect on public health. Therapeutic vaccination against cancer is more challenging but, armed with new immunological insight and genetic technology, aims similarly to harness the power of the immune system, in this case to destroy or suppress tumour cells.
2. Passively transferred antibodies and T cells are clearly able to attack human cancer cells in vivo and are included in treatment protocols for some cancers. Active vaccination would generate these effector pathways, together with immunological memory that is able to continuously detect and remove any emergent cancer cells.
3. Tumour antigens are being rapidly revealed, and can be expressed on cell surfaces or, more commonly, as peptides in association with the major histocompatibility complex class I (or II) molecules. DNA vaccines can be designed to activate antibody and/or T-cell responses, providing focused immune attack on selected antigens.
4. DNA vaccines offer a precise but flexible strategy for delivering antigens to the immune system, and additional sequences encoding molecules to manipulate outcome can be included. The problem of translating success in preclinical models to patients seems to be overcome by using electroporation, which dramatically improves performance and is now in clinical trials for prostate cancer.
5. The key to bypassing immune tolerance and activating high levels of anti-tumour antibody or cytotoxic T cells lies in inducing CD4⁺ T-cell help. Sequences derived from microbial antigens can be incorporated into anti-tumour DNA vaccines, a strategy which mobilizes help for anti-tumour responses from the large non-tolerized anti-microbial repertoire.
6. Clinical trials are the real test, but the current question is largely of efficacy rather than toxicity. New thinking is informing pilot trial design within a highly regulated environment, and immunological assays that can be predictors of clinical outcome are developing rapidly.

要点翻译：

1. 针对传染性病原体的预防性疫苗接种对公共健康产生了巨大影响。而针对癌症的治疗性疫苗则面临更大挑战，但在新的免疫学见解和基因技术的支持下，其目标同样是利用免疫系统的力量——在这种情况下是摧毁或抑制肿瘤细胞。
2. 被动转移的抗体和T细胞显然能够在体内攻击人类癌细胞，并已被纳入某些癌症的治疗方案。主动接种疫苗将激活这些效应通路，并产生免疫记忆，从而能够持续检测并清除任何新出现的癌细胞。
3. 肿瘤抗原正被迅速揭示，它们可以表达在细胞表面，或者更常见的是作为肽段与主要组织相容性复合物I类（或II类）分子结合。DNA疫苗可被设计用于激活抗体和/或T细胞反应，从而针对选定的抗原进行聚焦性免疫攻击。
4. DNA疫苗为向免疫系统递送抗原提供了一种精确而灵活的策略，并且可以加入编码分子的额外序列以调控免疫结果。通过使用电穿孔技术，临床前模型成功向患者应用的转化问题似乎得以克服——该技术显著提升了疫苗性能，目前正在进行前列腺癌的临床试验。
5. 克服免疫耐受并激活高水平抗肿瘤抗体或细胞毒性T细胞的关键在于诱导CD4+T细胞的辅助作用。源自微生物抗原的序列可被整合到抗肿瘤DNA疫苗中，这种策略能从庞大的非耐受性抗微生物库中调动对抗肿瘤反应的辅助力量。
6. 临床试验才是真正的考验，但目前的问题主要在于疗效而非毒性。在严格监管的环境下，新思维正在指导初步试验设计，同时能够预测临床结果的免疫检测方法也在快速发展。

英文摘要：

DNA vaccination has suddenly become a favoured strategy for inducing immunity. The molecular precision offered by gene-based vaccines, together with the facility to include additional genes to direct and amplify immunity, has always been attractive. However, the apparent failure to translate operational success in preclinical models to the clinic, for reasons that are now rather obvious, reduced initial enthusiasm. Recently, novel delivery systems, especially electroporation, have overcome this translational block. Here, we assess the development, current performance and potential of DNA vaccines for the treatment of cancer.

摘要翻译： 

DNA疫苗接种突然成为一种备受青睐的诱导免疫策略。基于基因的疫苗所提供的分子精确性，以及能够加入额外基因以引导和增强免疫力的便利性，一直颇具吸引力。然而，由于从临床前模型到临床的转化明显失败，原因如今已相当明显，最初的热情有所减退。近来，新型递送系统，尤其是电穿孔技术，已克服了这一转化障碍。在此，我们评估了DNA疫苗用于治疗癌症的发展、当前表现及其潜力。

原文链接：

DNA vaccines: precision tools for activating effective immunity against cancer