- 作者: Cheng-Tao Lin; Ya-Chea Tsai; Liangmei He; Roanne Calizo; Hung-Hsueh Chou; Ting-Chang Chang; Yung-Kuei Soong; Chien-Fu Hung; Chyong-Huey Lai
- 作者服務機構: 1 Department of Pathology, Johns Hopkins Medical Institutions, CRB II Rm. 307, 1550 Orleans Street. Baltimore, MD, 21231, USA; ; 2 Department of Oncology, Johns Hopkins Medical Institutions, CRB II Rm. 307, 1550 Orleans Street, Baltimore, MD, 21231, USA; ; 3 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chung Gung University College of Medicine, Taoyuan, Taiwan
- 中文摘要: --
- 英文摘要: The HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8+ T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8+ T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications.
- 中文關鍵字: --
- 英文關鍵字: Human Papillomavirus (HPV), E6, E7, DNA vaccines