Zahm Christopher D, Colluru Viswa Teja, McNeel Douglas G
Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI 53705, United States.
Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI 53705, United States.
Pharmacol Ther. 2017 Jun;174:27-42. doi: 10.1016/j.pharmthera.2017.02.016. Epub 2017 Feb 7.
DNA vaccines offer many advantages over other anti-tumor vaccine approaches due to their simplicity, ease of manufacturing, and safety. Results from several clinical trials in patients with cancer have demonstrated that DNA vaccines are safe and can elicit immune responses. However, to date few DNA vaccines have progressed beyond phase I clinical trial evaluation. Studies into the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to directly present or cross-present DNA-encoded antigens, and the activation of innate immune responses due to DNA itself, have suggested opportunities to increase the immunogenicity of these vaccines. In addition, studies into the mechanisms of tumor resistance to anti-tumor vaccination have suggested combination approaches that can increase the anti-tumor effect of DNA vaccines. This review focuses on these mechanisms of action and mechanisms of resistance using DNA vaccines, and how this information is being used to improve the anti-tumor effect of DNA vaccines. These approaches are then specifically discussed in the context of human prostate cancer, a disease for which DNA vaccines have been and continue to be explored as treatments.
由于其简单性、易于生产和安全性,DNA疫苗相对于其他抗肿瘤疫苗方法具有许多优势。多项针对癌症患者的临床试验结果表明,DNA疫苗是安全的,并且能够引发免疫反应。然而,迄今为止,很少有DNA疫苗进展到超过I期临床试验评估阶段。关于DNA疫苗作用机制的研究,涉及能够直接呈递或交叉呈递DNA编码抗原的抗原呈递细胞类型,以及DNA本身引起的先天免疫反应的激活,提示了增强这些疫苗免疫原性的机会。此外,关于肿瘤对抗肿瘤疫苗耐药机制的研究提出了可增强DNA疫苗抗肿瘤效果的联合方法。本综述重点关注使用DNA疫苗的这些作用机制和耐药机制,以及这些信息如何被用于提高DNA疫苗的抗肿瘤效果。然后,将在人类前列腺癌的背景下具体讨论这些方法,DNA疫苗一直并将继续被探索用于治疗这种疾病。