Lin Cheng-Tao, Tsai Ya-Chea, He Liangmei, Yeh Chun-Nan, Chang Ting-Chang, Soong Yung-Kuei, Monie Archana, Hung Chien-Fu, Lai Chyong-Huey
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chung Gung University College of Medicine, Taoyuan, Taiwan.
Immunol Lett. 2007 Dec 15;114(2):86-93. doi: 10.1016/j.imlet.2007.09.008. Epub 2007 Oct 16.
DNA vaccination has emerged as a promising strategy for cancer immunotherapy. However, since DNA vaccines have low immunogenicity, various strategies have been developed to enhance the potency of DNA vaccines. In the current study, we aim to determine whether the potency of the DNA vaccine encoding human papillomavirus type 16 (HPV-16) E7 antigen can be enhanced by IL-2. We have generated a DNA vaccine encoding IL-2 linked to HPV-16 E7 antigen. Our results indicate that the DNA vaccine encoding a fusion of IL-2 and E7 proteins generated the highest frequency of E7-specific CD8(+) T cells. We also found that the DNA vaccine encoding a fusion of IL-2 and E7 proteins generated the strongest protective as well as therapeutic anti-tumor effect against E7-expressing tumors. In addition, it was observed that CD8(+) T cells were mainly responsible for the antitumor effect generated by the DNA vaccine encoding a fusion of IL-2 and E7 proteins. Thus, we conclude that the linkage of IL-2 to HPV-16 E7 antigen significantly enhances the DNA vaccine potency against E7-expressing tumors. Our strategy may potentially be used in other antigenic systems to control infectious diseases and/or cancer.
DNA疫苗已成为一种有前景的癌症免疫治疗策略。然而,由于DNA疫苗的免疫原性较低,人们已开发出各种策略来增强DNA疫苗的效力。在本研究中,我们旨在确定白细胞介素-2(IL-2)是否能增强编码人乳头瘤病毒16型(HPV-16)E7抗原的DNA疫苗的效力。我们构建了一种编码与HPV-16 E7抗原相连的IL-2的DNA疫苗。我们的结果表明,编码IL-2与E7蛋白融合体的DNA疫苗产生E7特异性CD8(+) T细胞的频率最高。我们还发现,编码IL-2与E7蛋白融合体的DNA疫苗对表达E7的肿瘤产生了最强的保护性和治疗性抗肿瘤作用。此外,观察到CD8(+) T细胞主要负责编码IL-2与E7蛋白融合体的DNA疫苗产生的抗肿瘤作用。因此,我们得出结论,IL-2与HPV-16 E7抗原的连接显著增强了针对表达E7肿瘤的DNA疫苗效力。我们的策略可能潜在地用于其他抗原系统以控制传染病和/或癌症。