Departamento de Desarollo Biotechnológico, Instituto de Higiene, Universidad de la República, Montevideo, Uruguay.
Curr Gene Ther. 2010 Feb;10(1):56-76. doi: 10.2174/156652310790945566.
The design of efficient vectors for vaccine development and cancer gene therapy is an area of intensive research. Bacteria-based vectors are being investigated as optimal vehicles for antigen and therapeutic gene delivery to immune and tumour cells. Attenuated Salmonella strains have shown great potential as live vectors with broad applications in human and veterinary medicine. An impressively high, and still growing, number of reports published over the last two decades have demonstrated the effectiveness in animal models of Salmonella-based therapies for the prevention and treatment of infectious and non-infectious diseases, as well as cancer. Further, the recent dramatic expansion in knowledge of genetics, biology and pathogenesis of the bacteria allows more rational design of Salmonella constructs tailored for specific applications. However, only few clinical trials have been conducted so far, and although they have conclusively demonstrated the safety of this system, the results on immunogenicity are less than optimal. Thus, more research particularly in target species is required to bring this system closer to human and veterinary use. In this review we first describe some particularities of the bacteria and its relationship with the host that could be on the basis of its success as vector, and then summarize the different strategies used so far to develop Salmonella-based vaccines for infectious diseases as well as for non-traditional indications such as prion and Alzheimer disease vaccination. Finally, we review the many different approaches that employ Salmonella for the design of new therapies for cancer.
高效疫苗开发和癌症基因治疗载体的设计是一个研究热点。基于细菌的载体正被研究作为向免疫细胞和肿瘤细胞输送抗原和治疗基因的最佳载体。减毒沙门氏菌菌株作为活载体具有很大的潜力，在人类和兽医医学中有广泛的应用。在过去二十年中，发表了令人印象深刻的、数量仍在不断增加的报告，证明了基于沙门氏菌的疗法在预防和治疗传染病和非传染性疾病以及癌症方面的动物模型中的有效性。此外，最近对细菌的遗传学、生物学和发病机制的知识的急剧扩展，允许更合理地设计针对特定应用的沙门氏菌构建体。然而，到目前为止，只有少数临床试验已经进行，尽管它们已经明确证明了该系统的安全性，但免疫原性的结果并不理想。因此，需要更多的研究，特别是在目标物种中，以使该系统更接近人类和兽医的应用。在这篇综述中，我们首先描述了细菌及其与宿主的关系的一些特殊性，这些特殊性可能是其作为载体成功的基础，然后总结了迄今为止用于开发基于沙门氏菌的传染病疫苗以及非传统适应症（如朊病毒和阿尔茨海默病疫苗接种）的不同策略。最后，我们回顾了许多不同的方法，这些方法利用沙门氏菌设计癌症的新疗法。
