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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8066592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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