PURPOSE To determine the efficacy of the therapeutic DNA vaccine GX-188E for inducing regression of cervical intraepithelial neoplasia (CIN) 3. PATIENTS AND METHODS We conducted a prospective, randomized, multicenter, open-label, phase II clinical trial of GX-188E in CIN3 patients positive for human papillomavirus (HPV) type 16/18. The primary endpoint was to determine the histopathologic regression to ≤CIN1 at visit seven (V7; 20 weeks after the first GX-188E injection), and an extension study was pursued until visit 8 (V8; 36 weeks after the first GX-188E injection). HPV-sequencing analysis and an ex vivo IFNγ ELISpot assay were performed using the collected cervical biopsy and blood samples from patients. RESULTS In total, 72 patients were enrolled and underwent randomization. Of them, 64 patients were included in per-protocol analysis (V7) and 52 in extension analysis (V8). Our data showed 52% (33/64) of patients at V7 and 67% (35/52) of patients at V8 presented histopathologic regression after receiving the GX-188E injection. We found that 73% (V7) and 77% (V8) of the patients with histologic regression showed HPV clearance. HPV clearance and histopathologic regression were significantly associated at V7 and at V8. Compared with the measurements at V1 (baseline), the patients at V8 with HPV clearance showed significantly higher fold changes in their IFNγ ELISpot responses compared with those without HPV clearance. The HPV sequence analysis revealed that the HPV type 16 E6/E7 variants D25E, V83L, and N29S were inversely associated with histopathologic regression at V8. CONCLUSIONS GX-188E is an effective therapeutic vaccine against a cohort containing only CIN3 patients.

中文翻译：

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HPV DNA疫苗GX-188E在宫颈上皮内瘤变患者中的II期，前瞻性，随机，多中心，开放标签研究3。

目的确定治疗性DNA疫苗GX-188E诱导宫颈上皮内瘤变（CIN）消退的功效。3．患者与方法我们在GX-188E上进行了一项前瞻性，随机，多中心，开放标签，II期临床试验。对人乳头瘤病毒（HPV）16/18型呈阳性的CIN3患者。主要终点是在第7次就诊（V7；首次GX-188E注射后20周），确定组织病理学回归至≤CIN1，并进行延伸研究直至第8次就诊（V8；首次GX-188E注射后36周）。 ）。HPV测序分析和离体IFNγELISpot分析使用收集的宫颈活检和来自患者的血液样本进行。结果共有72例患者入选并随机分组。在他们当中 每个方案分析（V7）包括64例患者，扩展分析（V8）包括52例患者。我们的数据显示，接受GX-188E注射后，在V7的患者中有52％（33/64）和在V8的患者中67％（35/52）有组织病理学上的消退。我们发现组织学消退的患者中有73％（V7）和77％（V8）表现出HPV清除率。HPV清除率和组织病理学退化在V7和V8时显着相关。与V1（基线）的测量值相比，具有HPV清除率的V8患者与没有HPV清除率的患者相比，其IFNγELISpot反应表现出明显更高的倍数变化。HPV序列分析显示，HPV 16型E6 / E7型D25E，V83L和N29S变异与V8处的组织病理学退化呈负相关。