Abstract CT080: Clinical and immunologic results of a multi-center, randomized, double blind, phase II trial using poly-gamma-glutamic acid (γ-PGA) for women with cervical intraepithelial neoplasia 1 (CIN 1) and correlation of PD-1/PD-L1 tumor expression
Authors: Cho Hyun-Woong , Ouh Yung-Taek , Hong Jin Hwa , Lee Jae Kwan , Jeon Jae-Won , Sung Moon-Hee 
Published: August 2018

Abstract
Introduction : The poly-gamma-glutamic acid (γ-PGA) is a safe and edible polypeptide that is naturally synthesized by Bacillus subtilis 1 and has long been taken up as an ingredient of fermented soybean foods. The γ-PGA as a signaling regulator of Toll-like receptor 4 (TLR4), has been shown to enhance natural killer (NK) cell activity and inhibit tumors. Although CIN-1 typically represents transient infection, about 10% of CIN-1 is found to progress to CIN-3, and HPV infection persists and leads to high grade cervical dysplasia in some women with CIN-1. The aim of this study was to investigate the efficacy and safety of γ-PGA and impact γ-PGA on the immune system including PD-1 / PD-L1 in patients with CIN 1.
Material & Methods : We conducted a multi-center, randomized, double blind, placebo control, parallel designed, phase 2b study. Participants were randomly assigned to one of two groups: half received oral solution containing 1500 mg of γ-PGA; half received a placebo. Each participants took one dose every 24 hours for 4 weeks. Colposcopy with biopsy was assessed at the time of screening and 12 weeks. Blood samples were drawn at the initial treatment and at the 4th, 8th, 12th weeks after treatment. The primary endpoint of the study was histologic regression rate between screening and 12th weeks. The secondary endpoint were cytologic response rate, HPV clearance, change of immune responses and PD-1/PD-L1 expression.
Result From April 2013 to December 2015, 254 patients were screened and a total of 200 patients participated in the study. Of these, Of 101 women in γ-PGA group, 42 (42.4%) women experienced histologic regression, whereas 26 (27.1%) in the control group experienced histologic regression, showing statistically significant differences (p=0.018). In the γ- PGA group, HPV clearance was found in 37 (43.5%) of the 85 high-risk HPV infected patients, showing a meaningful difference compared to the control group showing HPV clearance of 20 (26.7%) out of 75 (p=0.026). However, there was no significant difference between the two groups in terms of cytologic regression rate and type specific clearance of HPV. The immunologic factors including NK cell activity, CD8 cell count and PD-1/PD-L1 expression, which are thought to be related to the therapeutic mechanism of γ- PGA, showed no significant difference between the two groups.
Conclusion : The γ-PGA enhance histologic regression in CIN-1 patients and showed the possibility of non-invasive medical treatment. In addition, γ-PGA has shown its potential as a treatment for high-grade CIN or cancer in the future as it has been shown to be effective against high-risk HPV infection.
Citation Format: Hyun-Woong Cho, Yung-Taek Ouh, Jin Hwa Hong, Jae Kwan Lee, Jae-Won Jeon, Moon-Hee Sung. Clinical and immunologic results of a multi-center, randomized, double blind, phase II trial using poly-gamma-glutamic acid (γ-PGA) for women with cervical intraepithelial neoplasia 1 (CIN 1) and correlation of PD-1/PD-L1 tumor expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT080.