The antiviral effect of poly-gamma-glutamic acid (γ-PGA) in HPV-positive patients.

e14623 Background: Poly-gamma-glutamic acid (γ-PGA), as a signaling regulator of Toll-like receptor 4 (TLR4), has been shown to induce innate immune responses. In previous non-clinical study, we showed that γ-PGA induces signaling pathway of Type 1 interferon, which consequently eliminates various viruses such as SARS, hepatitis C virus, influenza virus, etc. To evaluate the clinical efficacy of γ-PGA, we’ve investigated the antiviral effect of γ-PGA on human. In retrospective study to evaluate, the clinical significance of g-PGA treatment for vaginal intraepithelial neoplasia (VAIN), γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive VAIN. Since previous human studies showed the possibility of a drug, we have completed a phase I dose escalation study to determine the safety, tolerance and pharmacokinetics of γ-PGA in healthy adult male subjects. Methods: In the current study, we designed a human study of γ-PGA orally treated daily (75 mL) for 24 weeks to demonstrate the antiviral effect of γ-PGA in female HPV-positive patients. HPV viral load and cell-mediated immune responses were measured during 24 weeks to compare HPV clearance rates between the γ-PGA-treated group and the placebo-controlled group and to evaluate immunological parameters, respectively. Results: . In phase IIb clinical trial to evaluate the efficacy and safety of γ-PGA for the fertile women with cervical intraepithelial neoplasia grade 1 (CIN1) patients, regression rate by the treatment of γ-PGA was 45.65%, whereas the placebo controls were 30.23% in ITT group with statistically significance ( p= 0.0247). Conclusions: γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive CIN I.