Safety and efficacy of mucosal immunotherapy using human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine for the treatment of high-grade squamous intraepithelial lesion (HSIL): The study protocol of a randomized placebo-controlled clinical trial (MILACLE study)

Yuji Ikeda, Yukari Uemura, Mikiko Asai-Sato, Takehiro Nakao, Takahiro Nakajima, Takashi Iwata, Azusa Akiyama, Toyomi Satoh, Hideaki Yahata, Kiyoko Kato, Daichi Maeda, Daisuke Aoki, Kei Kawana

Research output: Contribution to journalArticle


We developed an HPV16 E7-expressing Lactobacillus-based therapeutic vaccine, IGMKK16E7, to elicit mucosal E7-specific TH1 cellular immune responses. This study aims to examine the safety and clinical efficacy of IGMKK16E7 on HPV16-positive high-grade squamous intraepithelial lesion (HSIL). This is a multicenter, placebo-controlled, double-blind randomized phase I/II trial to test the safety and efficacy of IGMKK16E7 against HPV16-positive HSIL. The groups will include placebo, low-dose (0.5 g/day), middle-dose (1 g/day), and high-dose (1.5 g/day) IGMKK16E7. The target sample size will be 41 patients per group, and our data on our former agent, GLBL101c, were used to calculate sample size for 70% power and an α level = 0.05. The primary endpoint is IGMKK16E7 safety and pathological regression at week 16, and the secondary endpoints are cytological regression and HPV16 E7 immunological response. This study protocol has been approved by the Japanese Pharmaceuticals and Medical Devices Agency. Patient enrollment will begin in May 2019.

Original languageEnglish
Pages (from-to)877-880
Number of pages4
JournalJapanese journal of clinical oncology
Issue number9
Publication statusPublished - 2019 Oct 15



  • design paper
  • high-grade squamous intraepithelial lesion (HSIL)
  • immunotherapy
  • mucosal immunity
  • phase I/II clinical trial

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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