A Phase II, Prospective, Randomized, Multicenter, Open-Label Study of GX-188E, an HPV DNA Vaccine, in Patients with Cervical Intraepithelial Neoplasia 3

Abstract

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). HPVsequencing analysis and an ex vivo IFNg 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 IFNg 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.

<p>Therapeutic Vaccines for HPV-Associated Malignancies</p>

“…BVAC-C consists of B cells and monocytes utilized as APCs, loaded with HPV16/18 E6/E7 peptides, and transfused back into patients with recurring or metastatic cervical cancer (NCT02866006). Data from the Phase I trial 108 showed that BVAC injection resulted in mild AEs, and no DLTs in patients with platinum-resistant recurrent cervical cancer. The overall response rate was 11%, and the median progression-free survival was 6.8 months.…”

“…Patients also exhibited increased activation of natural killer T (NKT) cells, NK cells, and HPV-specific T cells post-vaccination. 108…”

“…They found that 52% of the 72 patients enrolled had histopathologic regression of CIN3 by 20 weeks after the first injection, and 67% of the patients showed regression by 36 weeks after the first injection. 108 An additional Phase II trial is registered online (NCT02596243), but the status is unknown.…”

Plant-Derived Natural Compounds in Genetic Vaccination and Therapy for HPV-Associated Cancers

“…Flt3L and tpa are included in the fusion gene to promote antigen presentation and trafficking of the fused protein to the secretory pathway, respectively [ 54 ]. Recently, GX-188E was described to be highly efficacious in patients with grade 3 cervical intraepithelial neoplasia (CIN3) (NCT02139267) [ 55 ].…”

Newly Emerging Human Coronaviruses: Animal Models and Vaccine Research for SARS, MERS, and COVID-19

“…Since it was first reported that immunization of naked plasmid DNA encoding foreign protein induces an Ag-specific immune response in mammals in the early 1990s ( 164 ), DNA vaccines have been widely tested in various pathogen models. Although DNA vaccines have not been approved for humans to date, their immunogenicity and therapeutic effects have long been tested across various clinical trials for infectious diseases as well as human papillomavirus-mediated cervical intraepithelial neoplasia ( 165 166 ). DNA vaccines expressing full-length or truncated forms of SARS-CoV S protein induced humoral and cellular immunity, supplying protection against SARS-CoV infection in murine models ( 98 124 125 ).…”