Department of Obstetrics and Genecology, The Catholic University of Korea College of Medicine, Seoul, Korea.
Cancer Res Treat. 2005 Feb;37(1):63-70. doi: 10.4143/crt.2005.37.1.63. Epub 2005 Feb 28.
Human papillomavirus (HPV) infection has a significant role in cervical carcinogenesis, and HPV oncoprotein E7 plays an important part in the formation and maintenance of cervical cancer. Interleukin-12 (IL-12) has been reported to induce a cellular immune response, and to suppress the tumor growth and the E7 production. Here we describe the use of adenoviral delivery of the HPV 16 E7 subunit (AdE7) along with adenoviral delivery of IL-12 (AdIL-12) in mice with HPV-associated tumors.
Mice were injected with TC-1 cells to establish TC-1 tumor, and then they were immunized with AdIL-12 and/or AdE7 intratumorally. The anti tumor effects induced by AdIL-12 and/or E7 were evaluated by measuring the size of the tumor. E7-specific antibody and INF-gamma production in sera, and the T-helper cell proliferative responses were then measured. Cytotoxic T-lymphocyte (CTL) and T cell subset depletion studies were also performed.
Combined AdIL-12 and AdE7 infection at the tumor sites significantly enhanced the antitumor effects more than that of AdIL-12 or AdE7 single infection. This combined infection resulted in regression of the 9 mm sized tumors in 80% of animals as compare to the PBS group. E7-specific antibody and INF-gamma production in the sera, and the T-helper cell proliferative responses were significantly higher with coinfection of AdIL-12 and AdE7 than with AdIL-12 or AdE7 alone. CTL response induced by AdIL-12 and AdE7 in the coinjected group suggested that tumor suppression was mediated by mostly CD8+ and only a little by the CD4+ T cells.
IL-12 and E7 application using adenovirus vector showed antitumor immunity effects against TC-1 tumor, and this system could be use in clinical applications for HPV-associated cancer.
人乳头瘤病毒（HPV）感染在宫颈癌的发生中起重要作用，HPV 癌蛋白 E7 在宫颈癌的形成和维持中起重要作用。白细胞介素 12（IL-12）已被报道能诱导细胞免疫反应，并抑制肿瘤生长和 E7 的产生。在这里，我们描述了使用腺病毒载体递送 HPV 16 E7 亚单位（AdE7）和腺病毒载体递送白细胞介素 12（AdIL-12）在 HPV 相关肿瘤的小鼠中的应用。
将 TC-1 细胞注射到小鼠体内以建立 TC-1 肿瘤，然后用 AdIL-12 和/或 AdE7 进行肿瘤内免疫。通过测量肿瘤的大小来评估 AdIL-12 和/或 E7 诱导的抗肿瘤作用。然后测量血清中 E7 特异性抗体和 INF-γ的产生以及 T 辅助细胞的增殖反应。还进行了细胞毒性 T 淋巴细胞（CTL）和 T 细胞亚群耗竭研究。
与 AdIL-12 或 AdE7 单独感染相比，在肿瘤部位联合感染 AdIL-12 和 AdE7 显著增强了抗肿瘤作用。这种联合感染导致 9mm 大小肿瘤的 80%动物肿瘤消退，而 PBS 组无肿瘤消退。与 AdIL-12 或 AdE7 单独感染相比，AdIL-12 和 AdE7 联合感染的血清中 E7 特异性抗体和 INF-γ的产生以及 T 辅助细胞的增殖反应明显更高。AdIL-12 和 AdE7 在联合注射组中诱导的 CTL 反应表明，肿瘤抑制主要是由 CD8+细胞介导的，只有很少一部分是由 CD4+T 细胞介导的。
使用腺病毒载体的 IL-12 和 E7 应用显示出对 TC-1 肿瘤的抗肿瘤免疫效应，该系统可用于 HPV 相关癌症的临床应用。
