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

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-controll...

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Autores principales: Ikeda, Yuji, Adachi, Katsuyuki, Tomio, Kensuke, Eguchi-Kojima, Satoko, Tsuruga, Tetsushi, Uchino-Mori, Mayuyo, Taguchi, Ayumi, Komatsu, Atsushi, Nagamatsu, Takeshi, Oda, Katsutoshi, Kawana-Tachikawa, Ai, Uemura, Yukari, Igimi, Shizunobu, Osuga, Yutaka, Fujii, Tomoyuki, Kawana, Kei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066592/
https://www.ncbi.nlm.nih.gov/pubmed/33915901
http://dx.doi.org/10.3390/vaccines9040329
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author Ikeda, Yuji
Adachi, Katsuyuki
Tomio, Kensuke
Eguchi-Kojima, Satoko
Tsuruga, Tetsushi
Uchino-Mori, Mayuyo
Taguchi, Ayumi
Komatsu, Atsushi
Nagamatsu, Takeshi
Oda, Katsutoshi
Kawana-Tachikawa, Ai
Uemura, Yukari
Igimi, Shizunobu
Osuga, Yutaka
Fujii, Tomoyuki
Kawana, Kei
author_facet Ikeda, Yuji
Adachi, Katsuyuki
Tomio, Kensuke
Eguchi-Kojima, Satoko
Tsuruga, Tetsushi
Uchino-Mori, Mayuyo
Taguchi, Ayumi
Komatsu, Atsushi
Nagamatsu, Takeshi
Oda, Katsutoshi
Kawana-Tachikawa, Ai
Uemura, Yukari
Igimi, Shizunobu
Osuga, Yutaka
Fujii, Tomoyuki
Kawana, Kei
author_sort Ikeda, Yuji
collection PubMed
description 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 Lactobacillus-based vaccine with stronger immunogenicity than GLBL101c should be developed.
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spelling pubmed-80665922021-04-25 A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) Ikeda, Yuji Adachi, Katsuyuki Tomio, Kensuke Eguchi-Kojima, Satoko Tsuruga, Tetsushi Uchino-Mori, Mayuyo Taguchi, Ayumi Komatsu, Atsushi Nagamatsu, Takeshi Oda, Katsutoshi Kawana-Tachikawa, Ai Uemura, Yukari Igimi, Shizunobu Osuga, Yutaka Fujii, Tomoyuki Kawana, Kei Vaccines (Basel) Article 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 Lactobacillus-based vaccine with stronger immunogenicity than GLBL101c should be developed. MDPI 2021-04-01 /pmc/articles/PMC8066592/ /pubmed/33915901 http://dx.doi.org/10.3390/vaccines9040329 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ikeda, Yuji
Adachi, Katsuyuki
Tomio, Kensuke
Eguchi-Kojima, Satoko
Tsuruga, Tetsushi
Uchino-Mori, Mayuyo
Taguchi, Ayumi
Komatsu, Atsushi
Nagamatsu, Takeshi
Oda, Katsutoshi
Kawana-Tachikawa, Ai
Uemura, Yukari
Igimi, Shizunobu
Osuga, Yutaka
Fujii, Tomoyuki
Kawana, Kei
A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)
title A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)
title_full A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)
title_fullStr A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)
title_full_unstemmed A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)
title_short A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)
title_sort placebo-controlled, double-blind randomized (phase iib) trial of oral administration with hpv16 e7-expressing lactobacillus, glbl101c, for the treatment of cervical intraepithelial neoplasia grade 2 (cin2)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066592/
https://www.ncbi.nlm.nih.gov/pubmed/33915901
http://dx.doi.org/10.3390/vaccines9040329
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