Bhuyan Prakash K, Dallas Michael, Kraynyak Kim, Herring Timothy, Morrow Matthew, Boyer Jean, Duff Susan, Kim Joseph, Weiner David B
Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA.
Wistar Institute, Philadelphia, PA, USA.
Hum Vaccin Immunother. 2021 May 4;17(5):1288-1293. doi: 10.1080/21645515.2020.1823778. Epub 2020 Nov 11.
VGX-3100 is an investigational DNA-based immunotherapy being developed as an alternative to surgery and ablation for cervical High-Grade Squamous Intraepithelial Lesion (HSIL) with the aim of preserving reproductive health while treating precancerous disease. Response durability up to 1.5 y following dosing is now reported.Histologic regression and HPV16 and/or HPV 18 (HPV16/18) clearance were previously demonstrated in a randomized, placebo-controlled, double-blind trial and reported for 6 months after the last dose of VGX-3100 or placebo. The presence of HPV16/18, Pap smear diagnoses, and immunogenicity longer-term responses were assessed at 18 months after the last dose.91% (32/35) VGX-3100-treated women, whose cervical HSIL regressed and avoided excision at 6 months following study treatment completion, had no detectable HPV16/18 at 18 months following treatment completion. These results were comparable to those for women who received placebo and then later underwent surgery. For VGX-3100 recipients who regressed at 6 months following study treatment completion and avoided excision during the trial, Pap testing showed no HSIL recurrence at 18 months following VGX-3100 treatment. VGX-3100-induced cellular immune responses specific for HPV 16/18 E6/E7 remained higher than for placebo control recipients at 18 months.In women with cervical HSIL who responded to VGX-3100 and were able to avoid surgery, clinical outcomes were comparable to the placebo control group which underwent conventional surgical treatment. These findings extend the understanding of the durability of the treatment effect of VGX-3100 up to 1.5 y and support that VGX-3100 could be used as an alternative to surgery.
VGX-3100是一种基于DNA的研究性免疫疗法，正在开发用于替代宫颈高级别鳞状上皮内病变（HSIL）的手术和消融治疗，目的是在治疗癌前疾病的同时保留生殖健康。现在报告了给药后长达1.5年的反应持久性。先前在一项随机、安慰剂对照、双盲试验中证明了组织学消退以及HPV16和/或HPV 18（HPV16/18）清除，并在最后一剂VGX-3100或安慰剂后6个月进行了报告。在最后一剂后18个月评估HPV16/18的存在、巴氏涂片诊断和免疫原性长期反应。91%（32/35）接受VGX-3100治疗的女性，其宫颈HSIL在研究治疗完成后6个月消退并避免了切除，在治疗完成后18个月检测不到HPV16/18。这些结果与接受安慰剂然后接受手术的女性的结果相当。对于在研究治疗完成后6个月消退并在试验期间避免切除的VGX-3100接受者，巴氏试验显示在VGX-3100治疗后18个月没有HSIL复发。在18个月时，VGX-3100诱导的针对HPV 16/18 E6/E7的细胞免疫反应仍然高于安慰剂对照接受者。在对VGX-3100有反应并能够避免手术的宫颈HSIL女性中，临床结果与接受传统手术治疗的安慰剂对照组相当。这些发现扩展了对VGX-3治疗效果持久性长达1.5年的理解，并支持VGX-3100可作为手术替代方案的观点。 00 0可作为手术替代方案的观点。
