A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing <i>Lactobacillus</i>, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)

• Main Authors: Yuji Ikeda, Katsuyuki Adachi, Kensuke Tomio, Satoko Eguchi-Kojima, Tetsushi Tsuruga, Mayuyo Uchino-Mori, Ayumi Taguchi, Atsushi Komatsu, Takeshi Nagamatsu, Katsutoshi Oda, Ai Kawana-Tachikawa, Yukari Uemura, Shizunobu Igimi, Yutaka Osuga, Tomoyuki Fujii, Kei Kawana
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Vaccines
• Subjects: Human Papillomavirus (HPV); therapeutic vaccine; mucosal immunity; Cervical Intraepithelial Neoplasia 2 (CIN2); cervical cancer; lactobacillus-based vaccine
• Online Access: https://www.mdpi.com/2076-393X/9/4/329

Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV); high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy is available for CIN2-3 treatment. This study is a placebo-controlled randomized clinical trial of GLBL101c treatment for CIN2 in 40 patients with HPV16-positive CIN2 who were 1:1 randomized to receive GLBL101c (1 g/daily) or placebo for 5 days at 1, 2, 4, and 8 weeks. No differences were noted between the GLBL101c and placebo groups for patient background and adverse events. Moreover, no statistically significant difference was noted between the two groups at the primary endpoint, pathological regression after 16 weeks of the first oral dose; however, only in the GLBL101c group, two patients had complete regression (CR; regression to normal within 16 weeks). IFNγ production was significantly correlated with the number of spots identified by the interferon gamma enzyme-linked immunospot (IFNγ-ELISPOT) assay using cervical lymphocytes (CxLs) or peripheral blood mononuclear cells. In the two cases of CR, E7-specific Th1 immune responses were observed at week 16. Therefore, we concluded as a novel <i>Lactobacillus</i>-based vaccine with stronger immunogenicity than GLBL101c should be developed.