Yang Benjamin, Jeang Jessica, Yang Andrew, Wu T C, Hung Chien-Fu
a Department of Pathology ; Johns Hopkins University ; Baltimore , MD USA.
Hum Vaccin Immunother. 2014;10(11):3153-64. doi: 10.4161/21645515.2014.980686.
DNA vaccination has emerged as an attractive immunotherapeutic approach against cancer due to its simplicity, stability, and safety. Results from numerous clinical trials have demonstrated that DNA vaccines are well tolerated by patients and do not trigger major adverse effects. DNA vaccines are also very cost effective and can be administered repeatedly for long-term protection. Despite all the practical advantages, DNA vaccines face challenges in inducing potent antigen specific cellular immune responses as a result of immune tolerance against endogenous self-antigens in tumors. Strategies to enhance immunogenicity of DNA vaccines against self-antigens have been investigated including encoding of xenogeneic versions of antigens, fusion of antigens to molecules that activate T cells or trigger associative recognition, priming with DNA vectors followed by boosting with viral vector, and utilization of immunomodulatory molecules. This review will focus on discussing strategies that circumvent immune tolerance and provide updates on findings from recent clinical trials.
由于其简便性、稳定性和安全性,DNA疫苗已成为一种有吸引力的癌症免疫治疗方法。众多临床试验结果表明,DNA疫苗患者耐受性良好,不会引发重大不良反应。DNA疫苗成本效益也很高,并且可以反复给药以提供长期保护。尽管具有所有这些实际优势,但由于肿瘤中对内源性自身抗原的免疫耐受,DNA疫苗在诱导有效的抗原特异性细胞免疫反应方面面临挑战。已经研究了增强针对自身抗原的DNA疫苗免疫原性的策略,包括编码抗原的异种版本、将抗原与激活T细胞或触发联合识别的分子融合、先用DNA载体启动然后用病毒载体加强,以及使用免疫调节分子。本综述将重点讨论规避免疫耐受的策略,并提供近期临床试验结果的最新情况。